Scaffold-organized clusters and electronic devices made using such clusters

ABSTRACT

A method for forming arrays of metal, alloy, semiconductor or magnetic clusters is described. The method comprises placing a scaffold on a substrate, the scaffold comprising, for example, polynucleotides and/or polypeptides, and coupling the clusters to the scaffold. Methods of producing arrays in predetermined patterns and electronic devices that incorporate such patterned arrays are also described.

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims priority from prior U.S. provisionalapplications, Nos. 60/191,814, filed Mar. 24, 2000, entitledScaffold-Organized Metal, Alloy, Semiconductor and/or Magnetic Clustersand Electronic Devices Made Using Such Clusters; 60/226,720, filed onAug. 21, 2000, entitled Scaffold Organized Clusters; and 60/231,193,filed Sep. 7, 2000, entitled Scaffold Organized Clusters. These priorpending provisional applications are incorporated herein by reference.

ACKNOWLEDGMENT OF GOVERNMENT SUPPORT

[0002] This invention was made in part using funds provided by (1) theDepartment of Defense, Office of Naval Research, under contract numbersN00014-93-0618 and N00014-93-1-1120, and (2) the National ScienceFoundation, Grant No. DMR-9705343. The federal government may haverights in this invention.

FIELD

[0003] This invention concerns a method for forming organized arrays ofmetal, alloy, semiconductor and/or magnetic clusters for use in themanufacture of electronic devices, such as high-density memory storageand nanoelectronic devices.

BACKGROUND

[0004] Fundamentally new technologies are required to continueincreasing device integration density and speed. Conventionalmetal-oxide semiconductor-field-effect transistors soon will reachfundamental density and speed limits as a result of quantum mechanicaltunneling. In order to scale electronic device sizes down to nanometerdimensions, systems containing increasingly fewer numbers of particlesmust be considered.

[0005] The ultimate limit is a system in which the transfer of a singlecharge quanta corresponds to information transfer or some type of logicoperation. Such single-electron systems are presently the focus ofintense research activity. See, for example, Single Charge Tunneling,Coulomb Blockade Phenomena in Nanostructure, edited by H. Grabert and M.H. Devoret, NATO ASI Series B: Physics Vol. 294 (1992). These systemshave potential application to nanoelectronic circuits that haveintegration densities far exceeding those of present day semiconductortechnology. See, Quantum Transport in Ultrasmall Devices, edited by D.K. Ferry, H. L. Grubin, C. Jacoboni, and A. Jauho, NATO ASI Series B:Physics Vol. 342 (1995).

[0006] Single-electron transistors based on the concept of Coulombblockade are one proposed technology for realizing ultra-dense circuits.K. K. Likharev, Single-electron Transistors: Electrostatic Analogs ofthe DC SQUIDS,” IEEE Trans. Magn. 23:1142 (1987); and IBM J. Res. Dev.32:144 (1988). Coulomb blockade is the suppression of single-electrontunneling into metallic or semiconductor islands. In order to achieveCoulomb blockade, the charging energy of an island must greatly exceedthe thermal energy. To reduce quantum fluctuations the tunnelingresistance to the island should be greater than the resistance quantumh/e². Coulomb blockade itself may be the basis of conventional logicelements, such as inverters. Id.

[0007] Equally promising is the fact that the Coulomb blockade effectcan be used to pump charges one-by-one through a chain of dots torealize a frequency-controlled current source in which the current isexactly equal to I=ef, where f is the clocking frequency. See, L. J.Geerligs et al., Frequency-locked Turnstile Device for Single-electrons,Phys. Rev. Lett., 64:2691 (1990); and H. Pothier et al., Single-ElectronPump Based on Charging Effects, Europhys. Lett. 17:249 (1992). Suchturnstile devices are of fundamental interest as highly accurate currentstandards.

[0008] The clocking of charge through an array is also one model ofinformation storage. It is possible that computation may be based onswitching of currents rather than charge which, due to the extremeaccuracy of single-electron current sources, may be more robust towardsunwanted fluctuations than single-electron transistor-based circuits.

[0009] One of the most promising technologies for realizing terabytememories is founded on the principle of the Coulomb blockade. Yano etal. have demonstrated room temperature operation of single-electrondevices based on silicon nanocrystals embedded in SiO₂. K. Yano et al.,Room-Temperature Single-electron Memory, IEEE Trans. Electron. Devices,41:1628 (1994); and K. Yano et al., Transport Characteristics ofPolycrystalline-Silicon Wire Influenced by Single-electron Charging atRoom Temperature, Appl. Phys. Lett., 67:828 (1995). Recently, a fullyintegrated 8×8 memory array using this technology has been reported. K.Yano et al., Single-Electron-Memory Integrated Circuit for Giga-to-TeraBit Storage, IEEE International Solid State Circuits Conference, p.266-267 (1996).

[0010] Microelectronic devices based on the principle of Coulombblockade have been proposed as a new approach to realizing electroniccircuits or memory densities that go beyond the predicted scaling limitfor present day semiconductor technology. While the operation of Coulombblockade devices has been demonstrated, most operate only at greatlyreduced temperatures and require sophisticated nanofabricationprocedures. The size scales necessary for Coulomb blockade effects atsuch relatively elevated temperatures of about room temperature imposelimits on the number, uniformity and connectivity of quantum dots. As aresult, alternative methodologies of nanofabrication need to beinvestigated and developed.

SUMMARY

[0011] The present invention provides a new process for making arrayscomprising metal, alloy, semiconductor and/or magnetic clusters. An“array” can be any arrangement of plural such clusters that is usefulfor forming electronic devices. Three primary examples of uses for sucharrays are (1) electronic circuits, (2) arrangements of computer memoryelements, both of which can be in one or several planes, and (3)sensors.

[0012] “Clusters” as used herein refers to more than one, and typicallythree or more, metal, alloy, semiconductor or magnetic atoms coupled toone another by metal-type bonds or ionic bonds. Clusters areintermediate in size between single atoms and colloidal materials.Clusters made in accordance with the present invention also are referredto herein as “nanoparticles.” This indicates that the radius of eachsuch cluster is on the order of about one nanometer. A primary goal ofthe present invention is to provide electronic devices that operate ator about room temperature. This is possible if the cluster size is madesmall enough to meet Coulomb blockade charging energy requirements atroom temperature. While cluster size itself is not dispositive ofwhether the clusters are useful for forming devices operable at or aboutroom temperature, cluster size is nonetheless quite important. Itcurrently is believed that clusters having radii much larger than abouttwo nanometers likely will not be useful for forming electronic devicesthat operate at or about room temperature.

[0013] The metal, alloy, semiconductor and/or magnetic clusters arebonded to “scaffolds” to organize the clusters into arrays. “Scaffolds”are any molecules, including polymers, that can be placed on a substratein predetermined patterns, such as linear bridges between electrodes,and to which clusters can be bonded to provide organized cluster arrays.Without limitation, scaffolds include biomolecules, such aspolynucleotides, polypeptides, and mixtures thereof. Polypeptidescapable of forming α-helices are particularly useful scaffold-formingmolecules. Polypeptides that are capable of forming other secondarystructures, such as 3₁₀-helices, 7π-helices, and β-sheets may in certainembodiments serve as scaffolds. Polypeptides that are capable of formingrepetitive higher order structures (i.e., tertiary, and quaternarystructures) may also serve as scaffolds. One example is the collagenhelix. Double stranded DNA, Holliday junctions, and RNA hairpins arenon-limiting examples of polynucleotide scaffolds.

[0014] One embodiment of a method for forming arrays of metal, alloy,semiconductor and/or magnetic clusters involves placing a scaffold on asubstrate, in, for example, a predetermined pattern. Arrays are formedby contacting the scaffold with plural, monodispersed (clusters ofsubstantially the same size) ligand-stabilized metal, alloy,semiconductor and/or magnetic clusters that couple to the scaffold. Ifthe clusters are metal clusters, then the metal may be selected from thegroup consisting of Ag, Au, Pt, Pd and mixtures thereof. If gold is themetal, the metal cluster may be Au₅₅.

[0015] Clusters may be coupled to a scaffold by ligand exchangereactions. Each cluster, prior to contacting the scaffold, includesplural exchangeable ligands bonded thereto. The ligand-exchangereactions involve exchanging functional groups of the scaffold for atleast one of the exchangeable ligands of the cluster that is presentprior to contacting the scaffold with the clusters. Examples ofexchangeable ligands suitable for forming metal clusters in accordancewith the invention may be selected from the group consisting of thiols,thioethers (i.e., sulfides), thioesters, disulfides, sulfur-containingheterocycles, 1°, 2° and perhaps 3° amines, pyridines, phosphines,carboxylates, nitriles, hydroxyl-bearing compounds, such as alcohols,and mixtures thereof. Thiols are particularly useful ligands forpracticing the present invention.

[0016] Clusters may also be coupled to the scaffold by electrostaticinteractions between the cluster and the scaffold. For example, clustersmay include plural ligands that possess a charge or charges, eitherpositive or negative, that serve to attract the clusters to oppositelycharged scaffolds. In one embodiment, the cluster includes ligandshaving at least one positive charge and the scaffold is a polynucleotidehaving plural negative charges along its phosphate backbone. In a moreparticular embodiment, the cluster includes ligands having quaternaryammonium groups. In another embodiment, the cluster includes ligandswith at least one negative charge, such as ligands having carboxylate orsulfonate group(s), and the scaffold is a polypeptide, such aspolylysine (PL), having plural positive charges. In a particulardisclosed embodiment, the scaffold is poly-L-lysine (PLL).

[0017] Clusters may be coupled to a scaffold through hydrophobicinteractions. In one embodiment, the cluster includes ligands with aportion that can intercalate into DNA. For example the portion may be ananthraquinone. Other examples of suitable intercalating portions includeplanar cations such as acridine orange, ethidium, and proflavin. In someembodiments, the portion facilitates intercalation at particular,sequence-specific sites within a DNA molecule. In other embodiments theclusters are coupled to a scaffold through covalent bonds between theligands of the cluster and the scaffold.

[0018] There are several methods for placing a scaffold onto a substratein predetermined patterns. For example, one method comprises aligningscaffold molecules in an electric field created between electrodes onthe substrate. It therefore will be appreciated that the scaffoldmolecules advantageously have a dipole moment sufficient to allow themto align between the electrodes. This is one reason why polypeptidesthat form α helices are particularly useful. The α-helix structureimparts a sufficient dipole to the polypeptide molecules to allowalignment of the molecules between the electrodes upon formation of anelectrical field. One example of a polypeptide useful for formingscaffolds in accordance with the present invention is polylysine.Similarly, polynucleotides, such as DNA, that assume helical structuresmay be aligned by electric fields.

[0019] Another method of patterning scaffold molecules comprisespolymerizing monomers, oligomers (10 amino acids or nucleotides orless), or small polynucleotides or polypeptides into longer molecules onthe surface of a substrate. For example, scaffold molecules can bepolymerized as a bridge between electrodes on a substrate.

[0020] Yet another method of placing a scaffold onto a substrate in apredetermined pattern is by anchoring the scaffold and inducingalignment of the anchored scaffold in a particular direction by fluidflow. For example, a scaffold may be aligned between two electrodes byattaching the scaffold to a first electrode and using fluid flow in thedirection of a second electrode to align the scaffold with the directionbetween the two electrodes. In a particular embodiment, the substrate ismica, the scaffold is DNA, and the DNA is attached to the firstelectrode using a thiol linkage. Fluid-induced alignment is used toalign the scaffold in the direction of the second electrode, and the DNAscaffold is bound to the mica substrate by Mg²⁺ ions, thereby holdingthe DNA in its aligned position. Fluid-induced alignment may also besubsequently used to align additional scaffolds so that they cross, orintersect scaffolds already aligned on the substrate.

[0021] Other methods of placing a scaffold onto a substrate in apredetermined pattern include positioning the scaffold on a substrateusing magnetic fields, optical tweezers, or laser traps. Multiplescaffolds may be arranged on a substrate using any of the above methods.Scaffolds may not only be aligned between electrodes but may also bealigned such that they cross or otherwise contact each other to formone-, two- or three-dimensional structures useful as templates forforming electronic devices comprising cluster arrays. Such clusterarrays may be used to provide high density electronic or memory devicesthat operate on the principle of Coulomb blockade at ambienttemperatures.

[0022] The present invention also provides compositions that are useful,for example, for forming metal, alloy, semiconductor and/or magneticcluster arrays. In a particular embodiment, the composition comprisesmonodispersed, ligand-stabilized Au₅₅ metal clusters coupled to apolypeptide in the shape of or capable of forming an α-helix with themetal clusters bonded thereto. In another embodiment, the compositioncomprises monodispersed, ligand stabilized gold metal clusters coupledto a polynucleotide capable of forming a helical structure. Inparticular embodiments, the metal clusters have metal-cluster radii offrom about 0.4 nm to about 1.8 nm, such as from about 0.4 nm to about1.0 nm.

[0023] In particular embodiments, the present invention includescompositions comprising a polypeptide capable of forming α-helix andplural monodispersed, ligand-stabilized metal and/or semiconductorclusters, each cluster having plural ligands that serve to couple theclusters to the polypeptide. In more particular embodiments, the pluralligands of the clusters interact with the polypeptide by an interactionselected from the group consisting of ligand exchange reactions,electrostatic interactions, hydrophobic interaction, and combinationsthereof. In other more particular embodiments, the metal and/orsemiconductor clusters have radii of from about 0.4 nm to about 1.8 nm,such as between about 0.4 nm and about 1.0 nm. If the clusters comprisemetal clusters the metal may be selected from the group consisting ofAu, Ag, Pt, Pd and mixtures thereof, and in particular embodiments theclusters may comprise Au₅₅ metal clusters.

[0024] Compositions comprising polynucleotides capable of forminghelical structures and plural monodispersed, ligand-stabilized metaland/or semiconductor clusters, where each cluster having plural ligandsserves to couple the clusters to the polynucleotide are also provided bythe invention. The plural ligands of the clusters may serve to interactand couple the cluster to the polynucleotide through interactions suchas ligand exchange reactions, electrostatic interactions, hydrophobicinteractions, intercalation reactions and combinations thereof.

[0025] In particular embodiments the invention provides organized arraysof metal clusters comprising monodispersed, ligand-stabilized metalclusters having metal-cluster radii of from about 0.4 nm to about 1.8nm, the metal being selected from the group consisting of Ag, Au, Pt, Pdand mixtures thereof. Such arrays include a scaffold and the metalclusters are coupled to the scaffold to form the organized array.

[0026] The present invention further provides an electronic device thatoperates at or about room temperature based on the Coulomb blockadeeffect. Such electronic devices include a first cluster (e.g. a clustercomprising a metal cluster core having a radius of between about 0.4 nmand about 1.8 nm) and a second such cluster. The clusters are physicallyspaced apart from each other at a distance of less than about 5 nm bycoupling the clusters to a scaffold, such as a biomolecular scaffold, sothat the physical separation between the clusters is maintained.Electronic devices according to the invention may also include pairs ofbiomolecular scaffolds, each with coupled clusters, arranged so that thescaffolds intersect to provide electric circuit elements, such assingle-electron transistors and electron turnstiles. Such elements maybe useful as components of chemical sensors or ultrasensitiveelectrometers. Because of their unique architecture, electronic devicesaccording to the invention exhibit a linear increase in the number ofelectrons passing between pairs of clusters as the potential differencebetween the two clusters is increased above a threshold value.

[0027] The present invention also provides methods of formingmonodispersed phosphine-stabilized gold nanoparticles that allow theradii of nanoparticles to be controllably adjusted. In one embodiment,the method comprises dissolving HAuCl₄ and PPh₃ in a biphasic system(for example, a biphasic system comprising a water phase, an organicphase, and a phase transfer catalyst) and adding sodium borohydride tothe biphasic system. In particular embodiments, the biphasic system maycomprise water and an organic solvent selected from the group consistingof toluene, xylenes, benzene, and mixtures thereof. The phase transfercatalyst may be a quaternary ammonium salt, for example,tetraoctylammonium bromide. Control of the nanoparticle size may beaccomplished through control of the rate at which sodium borohydride isadded to the biphasic system.

[0028] The invention also provides methods of preparing thiol-stabilizedgold nanoparticles. Thiol-stabilized gold nanoparticles may be preparedby dissolving phosphine-stabilized gold nanoparticles in an organicsolvent and exchanging the phosphine ligands of the phosphine-stabilizedgold nanoparticle for thiol ligands. Particles that are particularlyuseful for preparing arrays according to the invention are prepared fromthiol ligands that comprise a group or groups of atoms that are capableof coupling thiol-stabilized gold nanoparticle to scaffolds. Phosphineand thiol ligands may be prepared in a single-phase system if the thiolligand is soluble in an organic solvent. However, if the thiol ligand(s)is water soluble, it is still possible to exchange thiol ligands forphosphine ligands at the interface between a water-immiscible organicsolvent containing the phosphine stabilized gold nanoparticles and watercontaining the thiol ligand(s).

BRIEF DESCRIPTION OF THE DRAWINGS

[0029]FIG. 1 is a schematic diagram of an interdigitated electrode arrayhaving saw-tooth edges.

[0030]FIG. 2 is a schematic representation of a poly-L-lysine scaffoldhaving thiophenolate-stabilized nanoparticles coupled thereto.

[0031]FIG. 3 is a schematic representation of one method forincorporating gate electrodes at the molecular level.

[0032]FIG. 4 shows UV-Vis spectra (in methylene chloride solution) ofgold clusters with the ligands (a) ODT, (b) Pth, and (c) MBP, and where(d) is starting material and (e) is a sample of larger ODT-stabilizedclusters.

[0033]FIG. 5 is a TEM of ODT-stabilized clusters (aerosol-deposited frommethylene chloride solution onto a carbon-coated copper grid).

[0034]FIG. 6 is an electron micrograph of a patterned gold clusterstructure.

[0035]FIG. 7 is a graph illustrating current-voltage (I-V)characteristics of Au₅₅[P(C₆H₅)₃]₁₂Cl₆ at temperatures of 195 K, 295 Kand 337 K.

[0036]FIG. 8 is a graph illustrating observed current plateaus as afunction of the applied frequency at a temperature of 195 K, with theinset illustrating the plateau at f=0.626 MHz.

[0037]FIG. 9 is a graph illustrating current versus reduced voltage at atemperature of 195 K.

[0038]FIG. 10 is a graph illustrating current-voltage (I-V)characteristics of a poly-L-lysine scaffold decorated with11-mercaptoundeconic ligand-stabilized gold clusters.

[0039]FIG. 11 is a TEM image of a TEM grid having a poly-L-lysinescaffold decorated with 11-mercaptoundeconic ligand-stabilized goldclusters.

[0040]FIG. 12 is a representative TEM image showing nearly monodispersedtriphenylphosphine nanoparticle having a particle size of 1.4 nm±0.5 nm.

[0041]FIG. 13 is a background-subtracted graph of I-V characteristicsfor PLL films decorated with gold nanoparticles.

[0042]FIG. 14 is a conductance graph of the system of FIG. 13.

[0043]FIG. 15 is a 1×μm area showing mercaptoundecanoic acid-stabilizedgold nanoparticle arrays formed on mica substrates previously treatedwith PLL hydrobromide salt and soaked in dilute sodium hydroxidesolution until the PLL was no longer detectable by AFM.

[0044]FIG. 16 is a graph of voltage sweeps versus threshold voltage fora non-patterned sample versus a poly-L-lysine-patterned sample.

DETAILED DESCRIPTION Abbreviations and Definitions

[0045] The singular forms “a,” “an,” and “the” refer to one or moreunless the context clearly indicates otherwise.

[0046] PL—polylysine

[0047] PLL—poly-L-lysine

[0048] AFM—atomic force microscopy

[0049] TEM—transmission electron microscopy

[0050] SEM—scanning electron microscopy

[0051] XPS—x-ray photoelectron spectroscopy

[0052] ODT—octadecylthiol

[0053] TOABr—tetraoctylammonium bromide

[0054] Au₅₅—refers to gold nanoparticles prepared by the Schmidpreparation, having a diameter of approximately 1.4 nm.

[0055] The general steps used to produce organized arrays comprisingmetal, alloy, semiconductor and/or magnetic clusters in accordance withthe present invention include (1) attaching molecular scaffolds tosubstrates in predetermined patterns, (2) forming monodispersed,relatively small (i.e., nanoparticle size, with room temperature Coulombblockade applications typically using nanoparticles where the diameterof the core, d_(core) is less than about 2 nm) ligand-stabilized metal,alloy, semiconductor and/or magnetic clusters, (3) coupling theligand-stabilized clusters to the scaffolds to form organized arrays,(4) coupling electrical contacts to the organized arrays, and (5) usingsuch constructs to form electronic, particularly nanoelectronic,devices. The substrate generally is a metal, glass or semiconductormaterial.

[0056] Most efforts have been directed to developing working devicesusing metal clusters. Certain of the following passages therefore focuson describing how to make and use devices based on metal cluster arrays.It should be understood, however, that any reference in this applicationto “metal clusters” or “clusters” typically also refers to alloyclusters, semiconductor clusters, magnetic clusters, and combinationsthereof.

[0057] Important features of the present invention include the smallphysical size of the metal clusters, the ligand exchange chemistry andthe nature of the ligand shell produced by the ligand exchangechemistry. The small physical size of the metal clusters provides alarge Coulomb charging energy. The ligand-exchange chemistry provides ameans to tailor the ligand shell for a particular purpose and immobilizethe clusters on biomolecules. And, the ligand shell offers a uniform andchemically adjustable tunnel barrier between cluster cores.

[0058] The following paragraphs describe the present invention ingreater detail.

I. Forming Monodispersed Ligand-Stabilized Clusters

[0059] A feature of the present invention is the recognition thatmonodispersed, relatively small metal clusters can be used to developelectronic devices that operate at or about room temperature based onthe Coulomb blockade effect. “Monodispersed” refers to the formation ofa population of metal clusters of substantially the same size, i.e.,having substantially the same radii (or diameters). In contrast,prior-art approaches typically have used polydispersed metal clusterswhere the size of the metal clusters is not substantially uniform. Acompletely monodispersed population is one in which the size of themetal clusters is identical. However, complete monodispersity isdifficult, if not impossible, to achieve. And complete monodispersity isnot required to produce devices operating at room temperature based onthe Coulomb blockade effect. Nevertheless, as the dispersity of thecluster population proceeds from absolute monodispersity towardspolydispersity the likelihood that the device will operate reliably atroom temperature based on the Coulomb blockade effect decreases.

[0060] Moreover, as the radius of the metal cluster decreases, theintrinsic capacitance gets smaller. As capacitance gets smaller, thecharging energy of the cluster gets larger. Coulomb blockade effects areobserved when the charging energy exceeds the thermal energy at roomtemperature. Prior approaches have used clusters having radii generallylarger than would be useful for forming devices that operate at roomtemperature based on the Coulomb blockade effect. In contrast, thepresent invention forms metal “nanoparticles” having relatively smallradii. The size requirement for clusters made in accordance with thepresent invention can be established in at least two ways, (1) bystating absolute radius lengths, and (2) by comparing the radius of thecluster in question to the radius of gold clusters having magic numbers(see the discussion provided below) of gold atoms.

[0061] In terms of absolute numbers, “nanoparticle” is defined herein asa cluster having a radius of from about 0.4 nm to about 1.8 nm (4 Å toabout 18 Å), for example, from about 0.4 nm to about 1.25 nm (4 Å toabout 12.5 Å), such as from about 0.4 nm to about 1.0 nm (4 Å to about10 Å). These radius lengths refer solely to the radius of the metalcluster, and not the radius of the metal cluster and ligand sphere.

[0062] With its insulating ligand shell, the diameter of theligand-stabilized metal cluster can vary. The size of the ligand shellmay influence the electron tunneling rate between clusters. Tunnelingrate is exponentially related to the thickness of the ligand shell. As aresult, the diameter of the ligand shell may be tailored for aparticular purpose. It currently is believed that the diameters forligand-stabilized clusters useful for practicing the present inventionshould be from about 2.5 nm to about 5 nm. The relatively large metalclusters made previously do not provide a large Coulomb charging energyand do not operate at room temperature, and instead generally onlyoperate at temperatures of from about 50 mK to about 10 K.

[0063] “Bare” clusters, i.e., those without ligand shells, also may beuseful for practicing the present invention. For example, bare clusterscan be used to form electrical contacts.

[0064] Still another consideration is the distance between the edges ofmetal cluster cores. It currently is believed that the maximum distancebetween the edges of cluster cores for clusters useful for practicingthe present invention is about 5 nm (50 Å), and ideally is on the orderof from about 1 to about 2 nm (10-20 Å Å).

[0065] Originally it was believed that clusters in accordance with thepresent invention generally should include numbers of atoms that arebased on the so-called “geometric magic numbers” of atoms surrounded bya ligand shell. Geometric magic numbers result from the most denselypacked arrangement of atoms that form a “sphere.” Magic numbers aregiven by Formula 1 below $\begin{matrix}{1 + {\sum\limits_{n = 1}^{k}\left( {{10n^{2}} + 2} \right)}} & {{Formula}\quad 1}\end{matrix}$

[0066] where k is an integer that represents the number of shells ofmetal atoms surrounding a central atom. Noble metal clusters with k=2,4, 6, 7 and 8 have been synthesized and stabilized by a ligand shell.While clusters having magic numbers of atoms will work to practice thepresent invention, it has now been determined that magic numbers ofatoms likely are not required to provide clusters useful for practicingthe present invention.

[0067] Solely by way of example, metals used to form ligand-stabilizedmetal clusters in accordance with the present invention may be selectedfrom the group consisting of silver (Ag), gold (Au), platinum (Pt),palladium (Pd), and mixtures thereof. “Mixtures thereof” refers tohaving more than one type of metal cluster coupled to a particularscaffold, or different metal clusters bonded to different scaffolds usedto form a particular electronic device. It also is possible that metalalloy clusters, e.g., gold/palladium clusters, can be used to formcluster arrays and electronic devices in accordance with the presentinvention.

[0068] Gold is a particularly useful metal for forming ligand-stabilizedmonodispersed metal clusters. This is because (1) the ligand exchangechemistry for gold nanoparticles and the nature of the ligand shellformed about gold is well understood, (2) Au₅₅ has a diameter of about1.4 nm, which is particularly useful for forming organized metal arraysthat exhibit the Coulomb blockade effect at or about room temperature,and (3) it is possible to prepare nearly monodispersed gold clusterswithout lengthy purification requirements, such as lengthycrystallization processes.

[0069] Assuming that magic numbers do provide benefit, the magic numbersof gold, palladium and platinum atoms for use with the present inventionare 13, 55, 147 and 309. The magic number 55 is a particularly suitablemagic number (represented as Au₅₅, Pd₅₅ and Pt₅₅). The magic number ofsilver atoms for silver metal clusters useful for practicing the presentinvention may be the same as for gold.

[0070] Semiconductor materials may also be useful for practicing thepresent invention. Semiconductor materials that may be prepared asnanoparticles and stabilized with ligand spheres include, withoutlimitation, cadmium selenide, zinc selenide, cadmium sulfide, cadmiumtelluride, cadmium-mercury-telluride, zinc telluride, gallium arsenide,indium arsenide and lead sulfide.

[0071] Magnetic particles also may be used to decorate scaffolds inaccordance with the present invention. An example, without limitation,of such magnetic particles is iron oxide (Fe₂O₃).

II. Ligands

[0072] A. Background

[0073] Once a suitable metal, alloy, semiconductor and/or magneticmaterial is selected for forming nanoparticles, ligands for bonding tothe clusters also must be selected. The assembly of clusters intoCoulomb blockade structures requires molecular-scale organization of theclusters while simultaneously maintaining the insulating ligand spherebetween individual clusters. The clusters also should be coupled to thescaffold in a sufficiently robust manner to allow for fabrication ofdevices incorporating cluster arrays. This may be accomplished by ligandexchange reactions. The selection of ligands for forming an insulatingligand layer about the cluster and for undergoing ligand exchangereactions therefore is a consideration. Criteria useful for selectingappropriate ligands include, but are not limited to, (1) the ligands arecapable of coupling with the scaffold, such as through ligand-exchange,acid-base or intercalation reactions (2) the ligands increase thesolubility of the ligand-metal cluster complexes in organic solvents,thereby facilitating synthesis of metal clusters and subsequentreactions, and (3) the ligands form well ordered metal-ligand complexeshaving diameters that promote room temperature Coulomb-blockade effects.

[0074] B. Classes of Ligands

[0075] Ligands suitable for forming metal clusters in accordance withthe present invention may be selected, without limitation, from thegroup consisting of: thiols (RSH); thioethers (also known as sulfides,R—S—R′); thioesters (RCOSR); disulfides (R—S—S—R′); sulfur-containingheterocycles, such as thiophene; 1°, 2° and 3° amines (RNH₂, R₂NH andR₃N, respectively), particularly 1° amines; pyridines; phosphines (R₃P);carboxylates (RCO₂—); nitriles (RCN); hydroxyl-bearing compounds, suchas alcohols (ROH); and mixtures thereof. Additional guidance concerningthe selection of ligands can be obtained from Michael Natan et al.'sPreparation and Characterization of Au Colloid Monolayers, Anal. Chem.,67:735-743 (1995), which is incorporated herein by reference.

[0076] Organic sulfur-containing molecules (e.g., thiols, thioethers,thioesters, disulfides, sulfur-containing heterocycles, and mixturesthereof) are particularly useful class of ligands. Thiols, for example,are a suitable type of sulfur-containing ligand for several reasons.Thiols have an affinity for gold, which may be formed into electrodes orelectrode patterns. Moreover, thiols have been shown to be good ligandsfor stabilizing gold clusters. And, many thiol-based ligands arecommercially available. The thiols form ligand-stabilized metal clustershaving a formula M_(x)(SR)_(n) wherein M is a metal, R is an alkyl chainor aromatic group, x is a number of metal atoms that provide metalclusters having the characteristics described above, and n is the numberof thiol ligands attached to the ligand-stabilized metal clusters.

[0077] C. Organic Portion of Ligands

[0078] The organic portion of ligands useful for practicing the presentinvention also can vary. For example, the length of the alkyl chain canbe varied to obtain particular features desired in the ligand-stabilizedmetal clusters. These include the solubility of the metal clusters insolvents used to carry out the present invention, and the size andinsulating characteristics of the ligand-stabilized metal clusters.Alkyl chains having from about 2 carbon atoms to about 20 carbon atomsare particularly suitable for practicing the present invention.

[0079] Aryl-type ligands, i.e., aromatic groups such as phenyl rings,containing or having sulfur atoms coupled thereto also may serve asligands for forming ligand-stabilized metal clusters. For example,mercaptobiphenyl (HS-phenyl-phenyl) has been used to formligand-stabilized gold clusters. The aromatic rings of such compoundsmay further include functional groups capable of reacting with thescaffold molecules. For example, the aromatic rings may include acidicgroups, such as carboxylic acids, for acid-base reactions withfunctional groups of the scaffold molecules, such as amines.

[0080] Aromatic ligands are quite useful for producing rigid arrays,thereby stabilizing the electron transport properties. For this reason,aryl ligands currently are particularly useful ligands for practicingthe present invention. In addition, small alkyl groups, such asthioproprionic acid, also provide rigid ligand systems.

[0081] Ligands that intercalate into DNA also may be used, since thisprovides a convenient means for attaching clusters to DNA molecules.Typically, the DNA intercalating ligands include rigid n systems.Examples of such DNA intercalating ligands include, without limitation,anthraquinone, phenanthridinium, acridine orange, proflavin, ethidium,combinations thereof and derivatives thereof. DNA intercalating ligandsmay also be DNA-sequence dependent. Thus, DNA having particularsequences can be used as a scaffold that is intercalated atpredetermined portions of the scaffold. This provides a method forcontrolling and altering the spacing between metal clusters.

[0082] The ligands also can be inter-and/or intra-molecularlycrosslinked. For example, intercalating ligands may be photo-crosslinkedto the scaffold to provide more rigid systems.

[0083] Based on these considerations, a diverse family of functionalizednanoparticles has been prepared using a 1.4 nm core metal cluster[CORE]. Ligand exchange has used to prepare, from Au₅₅[P(C₆H₅)₃]₁₂Cl₆, awide variety of ligand stabilized clusters of the general formulasCORE-[PX₃]_(n), CORE-[S—X]_(b), and CORE-[NHX]_(n) where X serves tocouple the cluster to a scaffold and n is at least one. For example, Xmay include groups of atoms capable of acid-base reactions withscaffolds, groups of atoms capable of hydrophobic interactions withscaffolds, groups of atoms capable of intercalating in nucleic acids(e.g. DNA), groups of atoms capable of hydrogen bonding to scaffolds,groups capable of electrostatic interactions with scaffolds, and groupscapable of forming covalent bonds with a scaffold. Groups of atoms thatfacilitate interaction with scaffolds include, without limitation, alkylgroups from about C₃ to C₁₈, aryl groups, carboxylic acid groups,sulfonic acid groups, peptide groups, amine groups, and ammonium groups.Other functional groups that may be part of X include aldehyde groupsand amide groups.

[0084] Charged species are especially useful for electrostatic couplingof clusters to oppositely charged scaffolds. For example, ligands havingpositively charged quaternary ammonium groups have been made thatinteract strongly with anionic scaffolds, such as phosphate backbone ofDNA. Ligands having negatively charged sulfonate groups have been madefor interacting with positively charged scaffolds, such aspoly-L-lysine.

[0085] Specific examples of functionalized nanoparticles include:phosphine-based clusters of the formula CORE-(PR₃)_(n), where the Rgroups are independently selected from the group consisting of phenyl,cyclohexyl and alkane, for example, octyl, and n is at least one;amine-based clusters of the formula CORE-(NHR)_(n), where R is selectedfrom alkyl groups having 20 or fewer carbon atoms, for example,pentadecyl and n is at least one; and thiol-based clusters of theformula CORE-(SR)_(n) where the R group is selected from the groupconsisting of phenyl, biphenyl, alkyl groups having 20 or fewer carbonatoms, for example, propyl, hexyl, nonyl, undecyl, hexadecyl andoctadecyl, and n is at least one. Yet other examples include clusters ofthe formula CORE-[S—(CH₂)_(x)COOH]_(n), where x is between about 2 andabout 19 and n is at least one, for example, where x is equal to 2, 5,or 10; clusters of the formula CORE-[S—(CH₂)_(x)OH]_(n) where x isbetween about 2 and about 20 and n is at least one, for example, where xis equal to 2; clusters of the formula CORE-[S—(CH₂)_(x)NR₂]_(n) where Ris independently selected from the group consisting of hydrogen andC1-C4 alkyl, x is between about 2 and about 20 and n is at least one,for example, where x=2 and R is methyl; clusters of the formulaCORE-[S—(CH₂)_(x)NR₃ ⁺]_(n) where R is independently selected from thegroup consisting of C1-C4 alkyl, x is between about 2 and about 20, andn is at least one, for example, where x=2, and R is methyl; clusters ofthe formula CORE-[S—(CH₂)_(x)SO₃ ⁻]_(n) where x is between about 2 andabout 20, and n is at least one, for example, where x=2; clusters of theformula CORE-[S—(CH₂)_(x)CONH(CH₂)_(y)CH₃]_(n) where x+y is between 1and about 20 and n is at least one, for example, where x=2 and y=14;clusters with amino-acid containing ligands, including glycine-basedligands, such as CORE-[-S—(CH₂)₂COGlyGlyOH]_(n), and clusters havingintercalating ligands, such as shown below.

[0086] D. General Method for Producing Ligand-Stabilized Metal Clusters

[0087] The general approach to making ligand-stabilized metal clustersfirst comprises forming monodispersed metal clusters having displaceableligands. This can be accomplished by directly forming monodispersedmetal clusters having the appropriate ligands attached thereto, but ismore likely accomplished by first forming monodispersed,ligand-stabilized metal clusters which act as precursors for subsequentligand-exchange reactions with ligands that are more useful for couplingclusters to scaffolds.

[0088] One example, without limitation, of a monodispersed gold clusterthat has been produced and which is useful for subsequentligand-exchange reactions with the ligands listed above isAu₅₅[P(C₆H₅)₃]₁₂Cl₆. A procedure for making monodispersedAu₅₅[P(C₆H₅)₃]₁₂Cl₆ nanoparticles is provided by G. Schmid,Hexachlorodecakis(triphenylphosphine)-pentapentacontagold,Au₅₅[P(C₆H₅)₃]₁₂Cl₆ , Inorg. Syn., 27:214-218 (1990). Schmid'spublication is incorporated herein by reference. Schmid's synthesisinvolves the reduction of AuCl[PPh₃]. Example 1 below also discusses thesynthesis of Au₅₅[P(C₆H₅)₃]₁₂Cl₆. One advantage or Schmid's synthesis isthe relatively small size distribution of clusters produced by themethod, e.g., 1.4±0.4 nm.

[0089] Once ligand-stabilized monodispersed metal clusters are obtained,such clusters can be used for subsequent ligand-exchange reactions, aslong as the ligand-exchange reaction is readily facile and producesmonodispersed metal clusters. Prior to the present invention it was notappreciated that the Au₅₅[P(C₆H₅)₃]₁₂C₁₆ clusters could be used to formnearly monodispersed derivatives by ligand-exchange chemistry. In fact,some literature reports indicated that it was difficult, if notimpossible, to form linked metal clusters by ligand-exchange reactions.See, for example, Andres et al.'s Self-Assembly of a Two-DimensionalSupperlattice of Molecularly Linked Metal Clusters, Science,273:1690-1693 (1996).

[0090] To perform ligand-exchange reactions, a reaction mixture isformed comprising the metal cluster having exchangeable ligands attachedthereto and the ligands to be attached to the metal cluster, such asthiols. A precipitate generally forms upon solvent removal, and thisprecipitate is then isolated by conventional techniques. See Examples 2and 3 for further details concerning the synthesis of ligand-stabilizedmetals.

III. Molecular Scaffolds

[0091] A. Background

[0092] Metal clusters produced as stated above are coupled to molecularscaffolds. “Coupling” as used herein refers to some interaction betweenthe scaffold and the ligand-stabilized metal clusters such that themetal clusters become associated with the scaffold. Associated may meancovalently bound, but also can include other molecular associations,such as electrostatic interactions (including dipole-dipoleinteractions, charge-dipole interactions, and charge-chargeinteractions), and hydrophobic interactions. “Coupling” includesattaching clusters to scaffolds by (1) ligand exchange reactions wherefunctional groups of the scaffold molecules, such as sulfur-containingfunctional groups or amines, exchange with the ligands of themetal-ligand cluster, (2) acid-base type reactions between the ligandsand molecules of the scaffold, (3) intercalation of a ligand into anucleic acid (e.g., DNA) helix, and (4) electrostatic interactionsbetween charged clusters and oppositely charged scaffolds.

[0093] B. Scaffolds Comprising Biomolecules

[0094] To form useful electronic devices, the scaffolds areadvantageously disposed on a substrate in predetermined patterns towhich electric contacts can be made. The scaffolds of the presentinvention may comprise biomolecules, such as polynucleotides,polypeptides and mixtures thereof, and hence may be referred to asbiomolecular scaffolds. There is some precedent for usingpolynucleotides for forming molecular scaffolds. See, for example, C. A.Mirkin et al., A DNA-Based Method for Rationally AssemblingNanoparticles into Macroscopic Materials, Nature, 382:607 (1996); and A.P. Alivisatos et al., Organization of “Nanocrystal Molecules” using DNA,Nature, 382:609 (1996). Each of these references is incorporated hereinby reference. Polynucleotides provide a different spacing between metalclusters than do polypeptides. Thus, spacing between metal clusters canbe varied by changing the nature of the scaffold.

[0095] Polypeptides include polypeptides that form α-helical secondarystructures. Certain peptides, although attractive candidates from thestandpoint of being stabilizing ligands for the metal clusters, do notform α-helices. However, many polypeptides do form α-helices, and henceare good candidates for forming scaffolds in accordance with the presentinvention.

[0096] It also should be appreciated that the polypeptide can be a“homopolypeptide,” defined herein to refer to polypeptides having onlyone type of amino acid. One example of a homopolypeptide is polylysine.The free base form of polylysine readily forms an α-helix. Moreover,lysine provides a terminal amino group that is oriented favorably in theα-helix for ligand exchange reactions with the ligand-stabilized metalclusters. Homopolypeptides generally have been used in the practice ofthe present invention for several reasons. First, certainhomopolypeptides are commercially available, such as poly-L-lysine,poly-D-lysine, and poly-DL-lysine (available from Sigma, St. Louis,Mo.). Second, homopolypeptides provide more predictable α-helixformation with the side chains oriented outwardly from the α helix atknown, predictable distances. This allows the polypeptide to be designedfor a particular purpose.

[0097] The peptide also may be a “heteropolypeptide” (having two or moreamino acids), or block copolymer-type polypeptides (formed from pluraldifferent amino acids with identical amino acids being organized inblocks in the amino acid sequence), as long as such peptides containgroups that that facilitate coupling with metal clusters.

[0098] Most amino acids can be used to form suitable homo- orheteropolypeptides. Examples of particularly suitable amino acidsinclude, but are not limited to, naturally occurring amino acids such aslysine, arginine, tyrosine, and methionine; and nonnaturally occurringamino acids such as homolysine and homocysteine.

IV. Placing Scaffolds on Substrates

[0099] A. General Discussion

[0100] The scaffold simply may be placed on the surface of thesubstrate, in contrast to more tightly adhering the polypeptide to thesubstrate such as through electrostatic or covalent bonds. As usedherein, the term “substrate” refers to any material, or combination ofmaterials, that might be used to form electronic devices. For example,the substrate may be selected from the group consisting of silicon,silicon nitride, glass, plastics, insulating oxides, semiconductormaterials, quartz, mica, metals, and combinations thereof.

[0101] Simply placing the scaffold on the surface without consideringwhether to electrostatically or covalently bind the scaffold to thesubstrate simplifies the process for making working devices. Placing thescaffold on the surface of the substrate can be accomplished by (1)forming solutions containing the molecular scaffold, (2) placing thesolution containing the scaffold onto a substrate, such as by spincoating the solution onto a substrate, and (3) allowing the solvent toevaporate, thereby depositing the solid molecular scaffold onto thesubstrate surface. In this embodiment, the scaffold may adhere to thesubstrate by physisorption or chemisorptions.

[0102] If simple deposition of the scaffold onto the substrate does notproduce a sufficiently robust device, then the scaffold might be moretightly coupled to the substrate. One method for accomplishing this isto use compounds that act as adhesives or tethers between the substrateand the molecular scaffold. Which compounds to use as adhesives ortethers depends on the nature of the substrate and the metal cluster.For example, amino-silane reagents may be used to attach molecularscaffolds to the substrate. The silane functional group allows thetether to be coupled to a silicon, glass or gold substrate. Thisprovides a tether having a terminal amino group that can be used toreact with the scaffold to tether the scaffold to the substrate. Theterminal amino group also can be used as an initiation site for the insitu polymerization of polypeptides using activated amino acids. Anotherclass of tethers particularly useful for attaching polylysine tosubstrates is the co-carboxyalkanethiols (H—O₂C—R—SH). DNA may becoupled to mica by the addition of Mg²⁺ ions.

[0103] B. Organization of Scaffolds on Substrates

[0104] There are many methods for forming organized molecular arrays,particularly linear arrays, on the surface of substrates. One methodcomprises depositing dilute solutions of scaffold molecules ontosubstrates. A second method comprises aligning biomolecular scaffoldsbetween electrodes using an electric field. Another comprises growingpolypeptide chains between two or more electrodes beginning from aninitiation site placed on an electrode. Yet another comprisesflow-induced alignment of anchored scaffolds. Each of these approachesis discussed below and/or in the Examples that follow.

[0105] 1. Deposition from Dilute Solutions

[0106] Isolated molecular scaffolds can be prepared by depositing highlydilute solutions (i.e. dilute enough such that the scaffold moleculesare separated) onto substrate surfaces. Alternatively, this can beaccomplished by dilution of the molecular scaffold film with an inert,α-helix polypeptide such as poly-γ-benzyl-L-glutamate. See,Poly(γ-Benzyl-L-Glutamate) and Other Glutamic Acid Containing Polymers,H. Block (Gordon & Breach, NY) 1983.

[0107] 2. Aligning Scaffolds in an Electrical Field

[0108] A practical method, for providing aligned scaffolds on asubstrate employ an electrical field produced between two electrodes.FIG. 1 illustrates saw tooth electrodes 10 comprising electrodes 12-20that are placed on a substrate by conventional methods, such aselectron-beam lithography, UV-photolithography, charged particle beamlithography, thermal evaporation, or lift-off techniques. A solutioncomprising the scaffold molecules is first formed and then applied tothe surface of the substrate having the electrode pattern placedthereon, such as a substrate having the electrode pattern of FIG. 1.α-Helical polypeptides, for example, self-align (pole) in the presenceof an applied magnetic field or electrical field (typically 20 Vcm⁻¹).See, S. Itou, Reorientation of Poly-γ-benzyl-L-glutamate Liquid Crystalsin an Electric Field, Jpn. J. Appl. Phys., 24:1234 (1985). Presumablythis is due to their large diamagnetic anisotropy. See also, C. T.O'Konski et al, Electric Properties of Macromolecules IV. Determinationof Electric and Optical Parameters From Saturation of ElectricBirefringence in Solutions, J. Phys. Chem., 63:1558 (1959).

[0109] An electric field is generated between the electrodes, such asthe points of the saw tooth illustrated in FIG. 1. This local fieldbetween the two points causes the scaffold to align between the points.The solvent is evaporated to provide scaffolds oriented between theelectrodes.

[0110] Based on the above, it will be apparent that the dipole moment ofthe scaffold influences whether the scaffold may be oriented between thetwo electrodes, and the efficiency of the orientation. This is onereason why α-helical polypeptides are particularly useful polypeptidesfor forming scaffolds. The hydrogen bonds formed in the α-helix allorient in the same direction, thereby aligning the amide and carboxylgroups of the peptide backbone and imparting an overall dipole to thesecondary α helical structure. It currently is believed that the dipoleis primarily the result of the a helix, and not the side chains.

[0111] 3. Growing Polypeptides Between Electrodes

[0112] In some instances, it may be desirable to use scaffolds to bridgedirectly between two electrical contacts of interest. This can beaccomplished by first placing initiating sites on the electrodes, andthen “growing” polypeptides between the initiation sites on theelectrodes to form a bridge. One example of how this would beaccomplished is to attach a tether to an electrode, the tether having apendant functional group that is capable of forming peptide bonds whenreacted with an activated amino acid. The most likely pendant functionalgroup for this purpose is a 1° amine.

[0113] To provide a specific example to illustrate the procedure, atether comprising an alkyl chain having both a terminal amino group anda terminal sulfhydryl group (i.e., an amino-thiol, HS—R—NH₂) is reactedwith a gold electrode using conventional chemistry. This covalentlyattaches the sulfhydryl group of the tether to the metal (i.e.,Au—S—R—NH₂). The terminal amino group is then used to initiatepolymerization of a polypeptide using activated amino acids, perhaps inthe presence of an applied field, between the two electrodes. Thepolymerization is accomplished by supplying activated amino acids forreaction with the primary amine in a chain-growing reaction thatserially couples amino acids to the end of the growing chain andregenerates the primary amine for subsequent reaction with anotheractivated amino acid.

[0114] Activated amino acids are commercially available and aredescribed in the literature. Activated amino acids useful for growingpolypeptides include N-carboxyanhydride (NCA) amino acids. NCA aminoacids react with surface-bound initiator sites (e.g., the primary aminogroups) to begin a ring-opening polymerization of the NCA-amino acid.See, J. K. Whitesell et al., Directionally Aligned Helical Peptides onSurfaces, Science, 261:73 (1993). Whitesell's publication isincorporated herein by reference.

[0115] When NCA polymerization is performed under the influence of anelectric field applied between two electrodes it is possible to “grow”the polypeptide scaffolds from one electrode to another. One specificexample of an NCA amino acid that can be used for this purpose is thatderived from N-ε-benzyloxycarbonyl-L-lysine. The amino acid side chainsof this compound can be deprotected using trimethylsilyl iodide.Deprotection yields the poly-L-lysine scaffold.

[0116] Working embodiments of the present invention generally have usedpolylysine as the polypeptide useful for forming the molecular scaffold.Polylysine was chosen because it includes a hydrocarbon chain thatextends the amino functional group, which can undergoligand-displacement reactions with the ligand-stabilized metal cluster,out and away from the polypeptide backbone. Thus, two criteria that maybe used to select polypeptides for use as molecular scaffolds are (1)the ability of the polypeptide to form α helices, and (2) the presenceof side chains that provide functional groups which are metal-clusterstabilizing and capable of undergoing ligand-exchange reactions with theligand-stabilized metal clusters.

[0117] 4. Forming Polynucleotide Scaffolds

[0118] DNA also is a useful material for forming scaffolds, and has manyadvantages. For example, it is much easier to form long polynucleotidechains than to form polypeptide chains. Furthermore, DNA provides a morerigid material, and this is a beneficial attribute of scaffoldmaterials. Methods for providing polynucleotide scaffolds also recentlyhave been discovered. See, for example, (1) E. Braun et al., “DNATemplated Assembly and Electrode Attachment of a Conducting SilverWire,” Nature, p. 775 (1998); (2) N. Seeman, “DNA Components forMolecular Architecture,” Accounts of Chemical Research, 30:357 (1997);Qi J., et al. “Ligation of Triangles Built from Bulged 3-Arm DNABranched Junctions,” J. Am. Chem. Soc., 118:6121 (1996); and C. Niemeyeret al. “DNA as a Material for Nanotechnology,” Angewandte Chemie,International Edition in English, 36:585 (1997). Each of thesereferences is incorporated herein by reference. The Braun referenceprovides a method for positioning a DNA molecule between electrodesspaced by a particular distance, such as about 10 μm. Double strandedDNA, with single stranded sticky ends, and a pair of electrodes thathave single stranded DNA attached thereto that is complementary to thesequence of the sticky ends of the DNA are prepared. Annealing thesticky ends to the single-stranded primers allows coupling of doublestranded DNA between two electrodes spaced by a known distance.

[0119] There are other methods for positioning DNA scaffolds on asubstrate. For example, and without limitation, DNA may be manipulatedby: electric fields between two electrodes; attaching one end of a DNAstrand to an electrode, and then using solution flow toward anotherelectrode to align the DNA between the two electrodes; using opticaltweezers or laser traps to place the DNA in a particular alignment.

V. Decorating Scaffolds With Metal Clusters

[0120] To provide working electronic devices, clusters are coupled tothe scaffolds. FIG. 2 provides a schematic representation of apoly-L-lysine that is “decorated” with metal clusters, i.e., theclusters are coupled to the scaffold. A first consideration is whetherto decorate the scaffold with clusters prior to or subsequent to placingthe scaffold onto a substrate. Although both of these approaches work,there are some disadvantages with decorating the scaffold with theclusters prior to placing the scaffold on the substrate. This approachplaces clusters on all surfaces of the polypeptide, even those that comeinto contact with the underlying substrate. This is undesirable forseveral reasons. For example, such placement of the clusters mightinterfere with fixing the decorated scaffold to the substrate. And, itplaces clusters in locations in which they are not needed, and henceuses more valuable monodispersed clusters than needed.

[0121] Based on the above, a method which first places the scaffoldsonto a substrate, and subsequently decorates the scaffold with clustersis in most instances a more useful approach. This may be accomplished byfirst forming a solution comprising the ligand-stabilized monodispersedclusters using a solvent that does not dissolve the scaffold. Solventsfor this purpose include, without limitation, dichloromethane andhexanes. The ligand-stabilized clusters are then introduced onto thescaffold and allowed to undergo reactions with the scaffold molecules,such as ligand-exchange or acid-base type reactions, thereby couplingthe ligand-stabilized clusters to the scaffold. See Example 4 forfurther details concerning decorating scaffolds with clusters.

[0122] The present approach to producing decorated scaffolds also allowsfor good lateral definition, which is a key feature of the presentinvention. “Lateral definition” refers to the width of an array. Priorto the present invention, the state of technology was capable ofproducing lines having a width of about 300 Å. With the presentinvention, lateral resolution is much improved, and is on the order ofabout 10 Å. In addition, branched polypeptides offer the possibility ofintroducing control electrodes and interconnects at the molecular level.

VI. Ultrafast, Ultrahigh Density Switching Devices

[0123] This section discusses the steps required to use the decoratedmolecular scaffolds of the present invention to produce ultrafast,ultrahigh density switching devices. First, a substrate is selected andcleaned. One example of a substrate is a silicon nitride chip or wafer.On top of this substrate would be placed electrical contacts. This couldbe accomplished using known technologies, such as lithography or thermalevaporation of a metal, such as gold.

[0124] Once a substrate is obtained having the electrical contactsplaced thereon, a scaffold is then placed on the surface using thetechniques described above. Thereafter, the substrate with scaffold istreated with monodispersed, ligand-stabilized clusters to attach suchclusters to the scaffold. The organization of scaffold likely determinesthe particular device being made.

[0125] For a switching device, analogous to a transistor, saw toothelectrical contacts, such as those shown in FIG. 1, are deposited onto asubstrate and a scaffold then oriented therebetween. This provides twoarms of a transistor. A capacitance contact required to provide thethird arm of a transistor is imbedded in the substrate underneath themolecular scaffold. Direct electrical contact with this “gate” imbeddedin the substrate is not actually required.

[0126] Alternatively, a third contact arm could be incorporated into thetemplate. FIG. 3 is a schematic representation of a scaffold useful forthis purpose. For example, a polypeptide of a particular length, e.g., a25-mer or 50-mer, could first be coupled to an electrode. A branchingportion of the scaffold could then be attached, thereby forming anelectrical arm, or plural such arms, for further providing single ormultiple gate electrodes to the template. The scaffold is then coupledbetween two electrodes subsequent to the formation of this contact arm,or arms.

[0127] The method of the present invention can be used to form a varietyof standard circuit components to implement Boolean logic functions.These circuit components include, but are not limited to, AND, NAND,NOR, OR and Exclusive OR gates. Additionally, multiplexers andmuliplexer-based circuits can be created and used to implement Booleanlogic functions.

VII. Production and use of Phosphine-Stabilized Gold Nanoparticles

[0128] The present method provides the first new route to producingphosphine-stabilized gold nanoparticles since their first descriptionnearly twenty years ago. The described route is substantially simplerand safer than the traditional route, which involves the use of diboranegas (see Example 1, below). TEM, XPS and ligand (thiol) exchangereactions respectively reveal that the size, composition and reactivityof nanoparticles synthesized using this new method are comparable tothose produced by the traditional route. Additionally, this simple routecan produce large quantities of gold nanoparticles capped bytricyclohexylphosphine or trioctylphosphine, producing a novel class oftrialkylphosphine stabilized nanoparticles.

[0129] First described by Schmid in 1981, phosphine-stabilized goldnanoparticles, commonly referred to as gold 55, paved the way forinvestigating the properties of metal nanoparticles. The small size andlow dispersity of triphenylphosphine-passivated gold nanoparticlescontinues to make them important tools in the field of nanoelectronics,biological tagging, and structural studies. Recently the ability toexchange thiol ligands onto triphenylphosphine passivated nanoparticleswas demonstrated, which enabled the coupling of small size and lowdispersity with the stability of thiol-passivated gold. This has allowedinvestigation of applications that require both high stability and smallcore size, such as room temperature, Coulomb-blockade-basednanoelectronics. One embodiment of the present method provides aconvenient gram-scale synthesis of 1.4 nm triphenylphosphine stabilizednanoparticles that are comparable in both size and reactivity to thetraditional gold 55 nanoparticles (Example 8). This route utilizescommercially available reagents and replaces a hazardous reducing agent.The generality of this synthetic method has been explored through thesynthesis of previously unknown aliphatic, phosphine-stabilized goldnanoparticles, particularly trialkylphosphine stabilized nanoparticles.

[0130] A working embodiment of the synthesis is shown in Scheme 1.

[0131] With reference to Scheme 1, “a” refers to reaction conditions,including a toluene:water biphasic solvent system, tetraoctylammoniumbromide (see below), and a 5 hour reaction time, and “b” refers to theempirical formula of the resulting product, which is based upon size andatomic composition measurements.

[0132] Other suitable solvents for the method include benzene andxylenes. Useful phase transfer catalysts include quaternary ammoniumsalts of which tetraoctylammonium bromide is only and example.

[0133] Phosphine-stabilized gold nanoparticles produced by the methoddescribed herein can be used in any applications in which traditionallysynthesized gold nanoparticles are used. Such applications include, ofcourse, the construction of scaffold-organized clusters and electronicdevises including such clusters described in the present application. Inaddition, the aliphatic, phosphine-stabilized gold nanoparticles of thisinvention can be used as biological tags for (e.g., in electronmicroscopy or for the detection of positive associations on biologicalmicroarrays such as cDNA microarrays). Gold particles according to theinvention can be used, for instance, to label peptide molecules (Segondvon Banchet and Heppelmann, Histochem. Cytochem., 43, 821-827, 1995),proteins (for instance, antibodies or fragments thereof as described inHainfeld and Furuya, J. Histochem. Cytochem., 40:177-184, 1992); ornucleic acid molecules (such as hybridization probes), or liposomes(Hainfeld., Proc. An. Mtg, Micros. Soc. Am., San Francisco Press, SanFrancisco, Calif., pp. 898-899, 1996).

[0134] In certain embodiments, the gold nanoparticles of the inventioncan be used in combination with other labels, such as fluorescent orluminescent labels, which provide different means of detection, or otherspecific binding molecules, such as a member of thebiotin/(strept)avidin specific binding family (e.g., as described inHacker et al., Cell Vision, 4, 54-65, 1997).

VIII. EXAMPLES

[0135] The following examples are provided to illustrate certainparticular features of the present invention. These examples should notbe construed to limit the invention to the particular featuresdescribed.

Example 1

[0136] This example describes the syntheses of Au₅₅(PPh₃)₁₂Cl₆.Au[P(C₆H₅)₃]Cl was obtained from Aldrich Chemical Company. This compoundwas reduced using diborane (B₂H₆), which was produced in situ by thereaction of sodium borohydride (NaBH₄) and borontriflouride etherate[BF₃.O(C₂H₅)]. Au[P(C₆H₅)₃]Cl was combined with diborane in benzene toform Au₅₅(PPh₃)₁₂Cl₆. Au₅₅(PPh₃)₁₂Cl₆ was purified by dissolution inmethylene chloride followed by filtration through Celite. Pentane wasthen added to the solution to precipitate a black solid. The mixture wasfiltered and the solid was dried under reduced pressure to provideAu₅₅(PPh₃)₁₂Cl₆ in approximately 30% yield.

Example 2

[0137] This example describes the synthesis of Au₅₅(SC₁₈H₃₇)₂₆.Dichloromethane (˜10 ml), Au₅₅(PPh₃)₁₂Cl₆ (20.9 mg) and octadecylthiol(23.0 mg) were combined in a 25 ml round bottom. A black solution wasproduced, and this solution was stirred under nitrogen at roomtemperature for 36 hours. The solvent was then removed under reducedpressure and replaced with acetone. This resulted in the formation of ablack powder suspension. The solid was then isolated by vacuumfiltration and washed with acetone (10×5 ml). After the final wash, thesolid was redissolved in hot benzene. The benzene was removed underreduced pressure with gentle heating to yield a dark brown solid.

[0138] The solid material was then subjected to UV-VIS(CH₂Cl_(2, 230)-800 nm), ¹H NMR, ¹³C NMR, X-ray photoelectronspectroscopy (XPS) and atomic force spectroscopy. These analytical toolswere used to characterize the structure of the compound produced, andsuch analysis indicated that the structure of the metal-ligand complexwas Au₅₅(SC₁₈H₃₇)₂₆.

[0139] X-ray photoelectron spectroscopy (XPS) data also was collectedconcerning Au₅₅(SC₁₈H₃₇)₂₆. This involved irradiating molecules withhigh-energy photons of fixed energy. When the energy of the photons isgreater than the ionization potential of an electron, the compound mayeject the electron, and the kinetic energy of the electron is equal tothe difference between the energy of the photons and the ionizationpotential. The photoelectron spectrum has sharp peaks at energiesusually associated with ionization of electrons from particularorbitals. X-ray radiation generally is used to eject core electrons frommaterials being analyzed. Clifford E. Dykstra, Quantum Chemistry &Molecular Spectroscopy, pp. 296-295 (Prentice Hall, 1992).Quantification of the data provided by XPS analysis of Au₅₅(SC₁₈H₃₇)₂₆made according to this example showed that Au 4f comprised about 67.38%and S 2p constituted about 28.01%+4.17%, which suggests a formula ofAu₅₅(SC₁₈H₃₇)₂₆.

[0140] Quantification of XPS spectra gave a gold-to-sulfur ratio ofabout 2.3:1.0 and shows a complete absence of phosphorus or chlorine. Aswith Au₅₅(PPh₃)₁₂Cl₆, a broad doublet is observed for the Au 4f level.The binding energy of the Au 4f 7/2 level is about 84.0-84.2 eV versusthat of adventitious carbon, 284.8 eV. This indicates absence of Au(I)and is similar to binding energies obtained for clusters such asAu₅₅(PPh₃)₁₂Cl₆. The binding energy of the S 2p 3/2 peak ranges from162.4 to 162.6 eV for the series of clusters. These values are shiftedto lower energy than those found for free thiols (163.3-163.9 eV) andare close to the values reported for thiolates bound to gold(162.0-162.4 eV). ¹H and ¹³C NMR unambiguously rules out the possibilitythat unattached thiols may be present in the sample.

[0141] Thermal gravimetric analysis confirms the Au:S ratio obtainedfrom XPS. On heating to 600° C., ODT-stabilized clusters display a 40%mass loss, corresponding to 26 ODT ligands on an assumed 55-atom goldcluster. This ratio alludes to the retention of a small cluster size. Asample of the larger hexadecanethiol-stabilized gold cluster has beenshown to give a 33.5% mass loss, corresponding to from about 95 to about126 ligands per cluster (diameter=2.4 nm).

[0142] Optical spectra of gold colloids and clusters exhibit asize-dependent surface plasmon resonance band at about 520 nm (See FIG.4). In absorption spectra of ligand-exchanged clusters produced asstated in this example, the interband transition typically observed forsmall clusters including Au₅₅(PPh₃)₁₂Cl₆ was observed. Little or noplasmon resonance was observed, consistent with a cluster size of about1.7 nm or less. For the ODT-passivated cluster, no plasmon resonance wasobserved.

[0143] Quantitative size information can be obtained using transmissionelectron microscopy (TEM). The core size obtained from TEM images of theODT-stabilized cluster (FIG. 5) is found to be 1.7±0.5 nm and is in goodagreement with that obtained from atomic force microscope images.

[0144] Atomic force microscopy (AFM) also was performed on theAu₅₅(SC₁₈H₃₇)₂₆ produced according to this example. The analysisproduced a topographical representation of the metal complex. AFM probesthe surface of a sample with a sharp tip located at the free end of acantilever. Forces between the tip and the sample surface cause thecantilever to bend or deflect. The measured cantilever deflections allowa computer to generate a map of surface topography. Rebecca Howland etal., A Practical Guide to Scanning Probe Microscopy, p. 5, (ParkScientific Instruments, 1993). The AFM data showed heights of 1.5 nm forsingle clusters and aggregates subjected to high force. This correspondsto the size of the gold core clusters. This helped establish that thegold clusters of this example were close to the correct size for formingdevices in accordance with the present invention.

[0145] In a manner similar to that described above for Example 2, thiolstabilized structures also have been made using 1-propanethiol.

Example 3

[0146] This example describes the synthesis of Au₅₅(SPh—Ph)₂₅.Dichloromethane (˜10 ml), Au(PPh₃)₁₂Cl₆ (25.2 mg) and 4-mercaptobiphenyl(9.60 mg) were combined in a 25 ml round bottom. A black solution wasproduced, and this solution was stirred under nitrogen at roomtemperature for 36 hours. The solvent was removed under reduced pressureand replaced with acetone. This resulted in the formation of a blackpowder suspension. The solid was isolated by vacuum filtration andwashed with acetone (6×5 ml). The solvent was then removed under reducedpressure to yield 16.8 mg of a dark brown solid.

[0147] The solid material was subjected to UV-Vis (CH₂Cl_(2, 230)-800nm), ¹H NMR, ¹³C NMR, X-ray photoelectron spectroscopy (XPS) and atomicforce spectroscopy as in Example 2. This data confirmed the structureand purity of the metal complex, and further showed complete ligandexchange. For example, quantification of the XPS data made according tothis example showed that Au 4f comprised about 71.02% and S 2pconstituted about 28.98%, which suggests a formula ofAu₅₅(S-biphenyl)₂₅.

[0148] AFM analysis showed isolated metal clusters having measuringabout 2.5 nm which correlates to the expected size of the gold core witha slightly extended sphere.

[0149] Thiol-stabilized clusters as produced above display remarkablestability relative to Au₅₅(PPh₃)₁₂Cl₆, which undergoes decomposition insolution at room temperature to give bulk gold and AuCl[PPh₃]. Nodecomposition for the thiol-stabilized clusters was observed, despitethe fact that some samples were deliberately stored in solution forweeks. In other tests, the mercaptobiphenyl andoctadecylthiol-stabilized clusters (in the absence of free thiol) wereheated to 75° C. for periods of more than 9 hours in dilute1,2-dichloroethane solution with no resultant degradation. Underidentical conditions, Au₅₅(PPh₃)₁₂Cl₆ is observed to decompose to Au(O)and AuCl[PPh₃] within 2 hours.

Example 4

[0150] This example describes the electron transfer properties oforganometallic structures formed by electron-beam irradiation ofAu₅₅[P(C₆H₅)₃]₁₂Cl₆. This compound was produced as stated above inExample 1. A solution of the gold cluster was made by dissolving 22 mgof the solid in 0.25 mL of CH₂Cl₂ and 0.25 mL of 1,2-dichloroethane. Asupernatant solution was spin coated onto a Si₃N₄ coated Si wafer at1500 rpm for 25 seconds immediately after preparation. The film waspatterned by exposure to a 40 kV electron beam at a line dosage of 100nC/cm. The areas of the film exposed to the electron beam adhered to thesurface and a CH₂Cl₂ rinse removed the excess film. This procedureproduced well defined structures. See FIG. 6. These structures appearedto be smooth and continuous under SEM inspection. Attempts were made topattern the material using 254 nm UV lithography, but it was found to beinsensitive to this wavelength. The defined structures had dimensions assmall as 0.1 μm and AFM inspection measured the film thickness to be 50nm.

[0151] The organometallic samples were spin-coated with PMMA which waselectron-beam exposed and developed to define contact regions. Contactswere fabricated using thermal evaporation of 100 nm of gold andconventional liftoff procedures.

[0152] DC current-voltage (I-V) measurements of several samples weretaken. A shielded chamber, submerged in an oil bath, contained thesample mounted on a clean teflon stage. Rigid triaxial connections wereused to connect the sample to a constant DC voltage source andelectrometer. The oil bath temperature was controlled from 195 to 350 K.Thermal equilibrium was achieved with a 10 Torr partial pressure of Hein the chamber. Before electrical measurements the chamber was evacuatedto a pressure ˜10⁻⁵ Torr. The data showed little temperature drift overa typical four hour measurement sweep. The intrinsic leakage current ofthe system was measured using a control sample which had the samesubstrate and contact pad arrangement as the actual samples, but did nothave the organometallic between the pads. At room temperature, theleakage current was almost linearly dependent on bias over the range−100 to 100V, and had a maximum value ≦100 fA. While the ultimateresolution of the current measurement was 10 fA, the leakage current setthe minimum resolved conductance ˜10⁻¹⁵ Ω⁻¹. Constant amplitude RFsignals with frequencies, f, from 0.1 to 5 MHz, were applied to thesamples through a dipole antenna at 195 K. No attempt was made tooptimize the coupling between the RF signal and the sample.

[0153] Without RF, the I-V characteristics for one sample at severaltemperatures are shown in FIG. 7. As the temperature was reduced, thelow voltage portion of the curve flattened out and the current becameindistinguishable from the leakage current. Above an applied voltagemagnitude of 6.7±0.6 V, the current increased abruptly. The dataillustrated in FIG. 7 establishes that the monodispersed gold clusterscan produce devices that operate on the basis of the Coulomb blockageeffect. This can be determined from FIG. 7 because one of the curves haszero slope, indicating no current at the applied voltage, i.e., thecluster is blockaded at the particular temperature tested.

[0154] The application of the RF signal introduced steps in the I-Vcharacteristic, as shown in the inset to FIG. 8. FIG. 8 establishes thatan applied external varying signal (the frequency of which is providedby the X axis) actually controls the rate at which electrons movethrough metal clusters made in accordance with the present invention.The current at which these steps occurred was found to be proportionalto the applied signal frequency, as shown in FIG. 8. A least squaresanalysis of the linear current-frequency relationship for the highestcurrent step shown gives a slope 1.59±0.04×10⁻¹⁹ C.

[0155] The introduction of plateaus in the patterned sample I-Vcharacteristics is similar to the RF response reported in other Coulombblockade systems. This effect has been attributed to phase locking ofsingle-electron tunneling events by the external RF signal. When the nthharmonic of the applied frequency corresponds to the mth harmonic of thefrequency of tunneling in the system, mile, the current becomes lockedto a value I=(n/m)ef. The results obtained suggest that correlatedtunneling is present in the samples.

[0156] The patterned samples had stable I-V characteristics with timeand temperature. Furthermore, as the temperature was raised above about250 K the I-V characteristics developed almost linear behavior up toV_(T). The conductance below V_(T) was activated, with activationenergies E_(A) in the range 30-70 meV. One method to estimate thecharging energy from the activation energy is to use the argument thatthe charging energy for one island in a infinite two-dimensional array,E_(C)˜4E_(A). Assuming current suppression requires E_(c)≧10 kT, thesample with the largest activation energy should develop a Coulomb gapbelow ˜300 K. This value is within a factor of 2 of the measuredtemperature at which clear blockade behavior occurs in the patternedsamples. Given the accuracy to which E_(c) is known, the temperaturedependence of the conductance within the Coulomb gap is consistent withthe observation of blockade behavior. Using this value of E_(c), theeffective capacitance of a metal core in the patterned array is3×10⁻¹⁹F<C<7×10⁻¹⁹F. These values are close, but larger than theclassical geometric capacitance of an isolated Au55 clusterC=4πεε₀r˜2×10⁻¹⁹F, where the dielectric constant, ε, of the surroundingligand shell is expected to be ˜3. The agreement between the twoestimates of capacitance supports the notion that the currentsuppression in the metal cluster arrays is due to charging of individualAu₅₅ clusters.

[0157] The non-linear I-V characteristic is similar to that of either aforward biased diode or one-/two-dimensional arrays of ultra small metalislands or tunnel junctions. However, the dependence of the I-Vcharacteristic on the applied RF signal is not consistent withstraightforward diode behavior. Therefore, the data has been analyzed inthe context of an array of ultra small metal islands.

[0158] Several reports have discussed the transport in ordered arrays oftunnel junctions that have tunneling resistances greater than thequantum resistance h/e² and a charging energy significantly above thethermal energy. In this case Coulomb blockade effects introduce athreshold voltage below which current through the array is suppressed.As the applied voltage is increased well beyond threshold, thecurrent-voltage characteristic approaches a linear asymptote with aslope related to the tunnel resistance. With the same temperature andtunnel resistance constraints, Middleton and Wingreen have discussedone- and two-dimensional arrays of maximally disordered normal metalislands where disorder is introduced as random offset charges on eachdot. These authors predict current suppression below a threshold voltageand high bias current I˜(V/V_(T)−1)^(γ). Here, the threshold voltageV_(T) scales with the number of junctions N along the current direction.Analytically γ=1 for one-dimensional systems and 5/3 for infinitetwo-dimensional systems. Numerical simulations of a finitetwo-dimensional array gave γ=2.0±0.2.

[0159] While no effort was made to order samples, the data was analyzedusing both the ordered and the disordered models. The only consistentanalysis was found to be given by the disordered model. In particular,the high bias data did not have the linear asymptote predicted for anordered system, but did scale as expected for a disordered system, asshown in FIG. 9. FIG. 9 also shows that a two-dimensional array so thatsample is propagating through the sample tested along plural parallelpaths. Such an arrangement is important for developing memory storagedevices. The exponent γ˜1.6 which is closest to the analyticalprediction for an infinite, disordered two-dimensional array. From theanalysis the magnitude of V_(T)˜6±1 V which is in good agreement withthat estimated directly from the I-V data.

[0160] The introduction of steps in the I-V characteristics by a RFfield is similar to the RF response reported in other systems. Thiseffect has been attributed to phase locking of single-electron tunnelingevents by the external RF signal. If the applied frequency correspondsto a rational fraction multiple of the frequency of tunneling in thesystem, I/e, then the current is locked to a value I=(n/m)ef, where nand m are integers. Therefore, the linear relationships shown in FIG. 6between f and I suggests that correlated tunneling is present in thesamples. The lowest slope observed is best described with n/m=⅕. Forfrequencies up to 3 MHz, the current resolution is insufficient todistinguish between the ⅕ and ¼ harmonics. However, at higherfrequencies where it should have been possible to distinguish between ⅕and 1/4, the ¼ step was not observed.

[0161] At temperatures above about 250 K, the I-V characteristic wasalmost linear up to V_(T). In this regime the conductance was activated,with activation energies E_(A) in the range 30 to 70 meV for the samplesstudied. Similar activated behavior has been reported for tunneljunction systems. It was argued that for an infinite 2D array thecharging energy for one island E_(C)≈4E_(A). Applying this argument tothe present system, and assuming current suppression requires E_(C)≧10kT, the sample with the largest activation energy should develop aCoulomb gap below about 300 K. This estimate is within a factor of twoof the measured temperature at which clear blockage behavior is seen.Thus, the temperature dependence of the observed current within theCoulomb gap is consistent with the observation of blockade behavior.From the threshold voltage, V_(T)=αNe/C, and this estimate of E_(C), αNis approximately 10. The energy E_(C) can also be estimated if thecapacitance of an island is known. The capacitance of an isolated Au₅₅cluster is C=4πεε₀τ, where τ is the radius of the cluster and ε is thedielectric constant of the surrounding medium. The radius of a Au₅₅ is0.7 nm and the ligand shell is expected to have ε≈3, which C≈2×10⁻¹⁹F.The Coulomb charging energy, E_(C)=e²/2C≈340 meV which is within twentypercent of the maximum value of 4E_(A) found from the activation data.This result suggests that the current suppression is due to charging ofindividual Au₅₅ clusters.

[0162] Given the constraint that steps in the I-V characteristics areonly found when f<0.1/(R_(T)C), the fact that steps are seen up to f=5MHz gives the upper limit R_(T)<1×10¹¹ Ω. The differential resistanceobtained from the I-V characteristic well above threshold is anticipatedto be R_(diff)≈(N/M)R_(T), where M is the number of parallel channels.This estimate yields N/M≧30. From the sample dimensions and the size ofan individual cluster, a close packed array would have N/M˜5. Thisdisparity between the expected and experimentally derived values of theN/M suggests that the full width of the sample is not involved intransport. One explanation for the discrepancy in N/M may be that manyof the gold cores coalesce during sample fabrication so that transportis dominated by individual clusters between larger regions of gold.

Example 5

[0163] This example describes a method for making cluster arrays usingpoly-L-lysine as the scaffold and 11-mercaptoundeconic ligand-stabilizedmetal clusters. Prefabricated electrodes were drop-cast with a 2.2×10⁻⁵mol/l solution of 56,000 amu poly-L-Lysine.HBr in H₂O/CH₃OH. After a20-hour soak in 1% NaOH in nanopure water and a nanopure water rinse,the current-voltage characteristics of the sample were found to becomparable with that of a bare electrode. The polylysine coatedelectrode was then exposed to a drop of 11-mercaptoundeconicligand-stabilized gold clusters in DMSO (about 8 mg/l ml). After about20 minutes, the sample was subjected to a thorough rinse with DMSOfollowed by another rinse in methylene chloride. After correcting forthe leakage current of the bare electrode, the current-voltagecharacteristic of the sample were measured, as shown in FIG. 10.

[0164] A TEM grid was prepared as well using the polylysine scaffold andthe 11-mercaptoundeconic ligand-stabilized gold clusters in DMSO. Thepolylysine solution was drop cast onto TEM grids. A 20-hour soak in 1%NaOH was followed by a nanopure water rinse. The dry TEM grids were thenexposed to a drop of 11-mercaptoundeconic ligand-stabilized goldclusters in DMSO. After about twenty minutes, the grids were thoroughlyrinsed, first using DMSO and then using methylene chloride. Lines ofclusters can be seen in FIG. 11.

Example 6

[0165] This example describes how to make electrical connections tometal cluster arrays. Saw tooth interdigitated array (IDA) goldelectrodes are used and are made using electron beam lithography. Thegap between saw tooth points in the array will be approximately 200-300Angstroms. An omega-amino alkanethiol will be chemisorbed to the goldsurface and subsequently electrochemically desorbed from one set of theIDA fingers. An omega-NHS-ester alkylthiol will be attached to the bareset of fingers. A precursor to poly-L-lysine will be polymerized fromthe amino-modified fingers toward the NHS-ester fingers where thegrowing end will be captured. The side chains of the poly-L-lysine chainwill be deprotected and treated with carboxy-terminated goldnanoparticles to form the desired one-dimensional array. Gates will beincorporated either under the substrate or as an additional electrodenear (above) the surface of the device.

Example 7

[0166] This example describes a method for making phosphine-stabilizedgold nanoparticles, particularly 1.4 nm (±0.5 nm) phosphine-stabilizedgold nanoparticles. Traditional methods for making such molecules areknown, and are, for instance, described by G. Schmid (Inorg. Syn.,27:214-218, 1990) and in Example 1).

[0167] Scheme 1 (above) illustrates a convenient one-pot, biphasicreaction in which the nanoparticles can be synthesized and purified inless than a day from commercially available materials. Hydrogentetrachlorolaurate trihydrate (1.11 g, mmol) and tetraoctyl ammoniumbromide (1.8 g, mmol) were dissolved in a nitrogen sparged water/toluenemixture (100 mL each). Triphenylphosphine (2.88 g, 11.0 mmol) was added,the solution stirred for five minutes until the gold color disappeared,and aqueous sodium borohydride (2.0 g, 41.0 mmol, dissolved in 5 mLwater immediately prior to use) was rapidly added resulting in a darkpurple color (this addition results in vigorous bubbling and should beperformed cautiously). The mixture was stirred for three hours undernitrogen, the toluene layer was washed with water (5×100 mL) to removethe tetraoctylammonium bromide and borate salts and the solvent removedin vacuo to yield 1.3 g of crude product.

[0168] To effect further purification, the resulting solid was suspendedin hexanes, filtered on a glass frit, and washed with hexanes (300 mL)to remove excess triphenylphosphine. Washing with a 50:50 mixture ofmethanol and water (300 mL) removed triphenylphosphine oxide. Each ofthese washes was monitored by TLC and the identity of the collectedmaterial was confirmed by ¹H and ³¹P NMR. Pure samples were obtained byprecipitation from chloroform by the slow addition of pentane (to removegold salts, as monitored by UV-Vis and NMR). After purification, thisprocedure yielded 644 mg of purified nanoparticle product from 1.35 g ofhydrogen tetrachlorolaurate. In contrast, the traditional synthesisyields about 300 mg of purified nanoparticle product per 2 g hydrogentetrachlorolaurate.

[0169] For comparison of these nanoparticles to the products of thetraditional synthesis the newly synthesized nanoparticles were analyzedto determine size, atomic composition, and reactivity as describedbelow. The small size of the nanoparticles, which allows for examinationof Coulomb blockade phenomena at room temperature, is an importantconsideration for evaluating the effectiveness of the synthesis.

[0170] Direct evidence of nanoparticle size and dispersity is providedby transmission electron microscopy (TEM). TEM was performed on aPhilips CM-12 microscope operating at a 100 kV accelerating voltage.Samples were prepared by drop casting dilute methylene chloridesolutions onto 400-mesh nickel grids coated with carbon. Images wererecorded as photographic negatives, scanned, and processed using NIHimage software. A total of 1628 particles were examined from twoseparate synthetic runs, for the triphenylphosphine nanoparticles.Background noise and agglomerated nanoparticles were removed from themeasurements by removing core sizes of <0.5 nm and >3 nm from theanalysis.

[0171] A representative TEM (FIG. 12) shows nearly monodispersetriphenylphosphine nanoparticles with a size of 1.4 nm±0.5 nm. The FIG.12 insert is a bar graph showing particle size distribution on this TEM.The x axis of the inset is the size of the particles (measured in nm,starting at 0.75 nm and increasing by increments of 0.25 nm to 3 nm).The y axis of the inset represents the number of particles observed ineach size (beginning at zero and increasing by increments of 50 to 350particles). The size measurements in this TEM compare well with thetraditional synthesis, which yields 1.4 nm±0.4 nm particles.

[0172] UV/Vis spectroscopy, a technique that is representative of thebulk material, was used to confirm TEM size determinations. UV-visiblespectroscopy was performed on a Hewlett-Packard HP 8453 diode arrayinstrument with a fixed slit width of 1 nm using 1 cm quartz cuvettes.The absence of a significant surface plasmon resonance at 520 nmindicates gold nanoparticles that are <2 nm diameter. UV/Vis spectra ofnewly synthesized nanoparticles are dominated by an interbandtransition, with no significant plasmon resonance at 520 nm. Thisindicates that there is no substantial population of nanoparticlesgreater than 2 nm in size.

[0173] Atomic composition of the nanoparticles was determined using thecomplementary techniques of x-ray photoelectron spectroscopy (XPS) andthermogravimetric analysis (TGA) allowing further comparison totraditionally prepared nanoparticles. TGA was performed under a nitrogenflow with a scan rate of 5° C. per minute. XPS was performed on a KratosHsi operating at a base pressure of 10⁻⁸ torr. Samples were prepared bydrop-casting a dilute organic solution of the nanoparticles onto a cleanglass slide. Charge neutralization was used to reduce surface chargingeffects. Multiplexes of carbon, sulfur, and phosphorus were obtained by30 scans each. Binding energies are referenced to adventitious carbon at284.4 eV. Data was recorded with a pass energy of 20 eV. XPS spectraprovides an average composition of 71% gold, 26% carbon, 2.6% phosphine,and 0.7% chlorine, corresponding to molar ratios of 18 Au:108 C:4.3 P:1Cl. TGA indicates a mass ratio of 71% gold to 29% ligand, independentlyconfirming the ligand-to-ratio determined by XPS. For direct comparisonwith the nanoparticles made by traditional methods, an average empiricalformula was generated by assuming a core size of 55 gold atoms. Based onthis assumption, an average particle produced by the method of thepresent invention was formulated as Au₁₀₁(PPh₃)_(12.5)Cl₃, in comparisonwith the Au₅₅(PPh₃)₁₂Cl₆ reported by Schmid. While thegold-to-phosphorus ratio matches that of the Schmid nanoparticles, thephosphorus-to-chlorine ratio of 4:1 is double that of the Schmidnanoparticles (2:1). This may be a reflection of thephosphorus-to-chlorine ratio in the starting materials of each reaction.

[0174] The reactivity of the nanoparticles to thiol ligand exchangefurther confirms their similarities to traditional triphenylphosphinestabilized nanoparticles. Using previously reported methods, a number ofstraight-chain alkanethiol and charged ω-Functionalized alkanethiolligands have been exchanged onto these nanoparticles. In eachthiol-for-phosphine ligand exchange reaction, there is little change inthe surface plasmon resonance of the UV/Vis spectra, indicatingnegligible size changes during the thiol for phosphine ligand exchange.Thus, the newly synthesized nanoparticles are similar in size, atomiccomposition, and reactivity to the Schmid preparation.

[0175] The disclosed methods have enabled the facile exploration ofvarious phosphine ligands that have previously not been explored.Substitution of PR₃ for PPh₃, and slight modification of the work-up,allows for isolation of alkyl-stabilized nanoparticles in good yield.Trioctylphosphine and tricyclohexylphosphine stabilized goldnanoparticles have been successfully synthesized, which appear to besubstantially larger by both UV-Vis. This approach apparently is thefirst reported synthesis of alkyl-phosphine stabilized goldnanoparticles. Further investigations regarding the effect of the Lewisbasicity of the ligand and the steric bulk of the ligand are underway.

[0176] This synthesis allows for the expansion of phosphine-stabilizednanoparticle materials. Large amounts of nanoparticle material can bemade in a single step using borohydride in place of diborane. Second,this synthesis allows for flexibility in the choice of phosphine ligandthat was previously unknown. Variation of ligand-to-gold ratios usingthe disclosed embodiments of the present invention can be used toachieve unprecedented size control of phosphine-stabilized goldnanoparticles.

Example 8

[0177] This example describes a method for determining the size of thenanoparticles made using a process similar to that described in Example8. Controlling the rate at which the reducing agent, such as sodiumborohydride, is added to the reaction mixture, can be used to makenanoparticles materials having desired core diameters, such as a goldcore diameter (d_(Core)<2 nm). The synthesis is the same in everyrespect as that stated in Example 8 except for the addition rate of thereducing agent (NaBH₄). In Example 8, NaBH₄ was added rapidly. In thispreparation the same quantity of reducing agent was added slowly (over aperiod of 10 minutes) from a dropping funnel fitted with a ground glassjoint and Teflon stopcock. The resultant nanoparticles were shown byUV-visible spectroscopy to have an average diameter of larger than 2 nm.

Example 9

[0178] This example describes the formation of gold nanoparticlenetworks fabricated between the fingers of gold, interdigitated arrayelectrodes having a 15 (or 1.5) or 2 μm gap by electrostatic assembly ofcarboxylic-acid-modified, gold nanonparticles onto the amino side chainsof the biopolymer poly-L-lysine (PLL). The samples were prepared asfollows. First, a 2.2×10⁻⁵ mol/l solution of poly-L-lysine-hydrobromidecomplex (54,000 amu) in 10/90% water/methanol was drop cast onto theelectrodes. The electrodes were pre-cleaned using a UV/ozone dry processfollowed by a rinse in nanopure water. The hydrobromide was removed fromthe amine side chains of the biopolymer by submerging the cast film in asolution of 1% sodium hydroxide in water for about 20 hours. The11-mercapto-undecanoic-acid-stabilized, gold nanoparticles weresynthesized from Schmid-Au₅₅ nanoparticles [see, G. Schmid, Inorg.Synth., 27, 214 (1990)] using ligand exchange. See L. O. Brown and J. E.Hutchison, J. Am. Chem. Soc., 119, 12, 384 (1997). Nanoparticledecoration of the biopolymer was accomplished by placing a concentratedsolution of the nanoparticles in dimethylsulfoxide onto thepoly-L-lysine film for about 20 minutes, after which it was rinsed indimethylsulfoxide and then dichloromethane. From the molecular weight,the average length of the poly-L-lysine was determined to be about 30nm. Therefore, each polymer accommodated about seven or eightnanoparticles.

[0179] Current-voltage (I-V) measurements were performed at roomtemperature with the samples in an electrically shielded vacuum chamber.See, L. Clarke, M. N. Wyboume, M. Yan, S. X. Cai, and J. F. W. Keana,Appl. Phys. Lett., 71, 617 (1997). Control measurements were made on thebare electrodes and again after the PLL had been deposited anddeprotonated. The I-V characteristics of the deprotonated PLL and thebare surface were linear (Ohmic) without any structure. Importantly,these two sets of control data were indistinguishable, which shows thatto within experimental uncertainty the surface conductance of the glasssubstrate was unaffected by the deprotonated PLL. In contrast, whendecorated with nanoparticles, the samples exhibited pronouncednon-linear I-V characteristics. After subtraction of the linear I-Vbehavior measured before PLL decoration, to within the measurementaccuracy the electrical characteristics showed a region of zeroconductance at low voltages. See FIG. 13. The onset of current ischaracterized by a threshold voltage, V_(T), that was found to bedifferent for different samples. Above the threshold, the currentincreases and the scaling Iα(V/V_(T)−1)^(γ) describes all sets of datawith γ=1.2±0.2. Here the error includes the uncertainty in the currentmeasurement and the spread between different data sets. At voltagesabove threshold, structure of period DV was observed in the I-V curvesof most samples, with the ratio ΔV/V_(T)˜2. This is most easily seen inthe conductance, as shown in FIG. 14. For this data the measuredthreshold voltage is V_(T)=12±1 V, and the period of the oscillations isΔV=25±3 V.

[0180] Thus, FIGS. 13 and 14 establish stable Coulomb blockade behaviorat room temperature. With reference to FIG. 13 and the I-Vcharacteristics of the disclosed systems, above the threshold voltagethe current is linear. Moreover, the conductance oscillations show thatthe systems are defect tolerant.

[0181] The value of the scaling exponent γ is indicative of theelectronic degrees of freedom in the sample. The values obtained for thetested materials are consistent with single-electron transport inone-dimensional systems where it is predicted that γ˜1. Thesepredictions are supported by measurements of the low-temperaturetransport in one-dimensional chains of lithographically-defined tunneljunctions that found γ=1.36±0.1. Further, the almost linear scaling isdistinct from the quadratic scaling reported for thin films containinggold nanoparticles. The current-voltage scaling, threshold behavior andperiodic structure are all reminiscent of single-electron behavior inone-dimensional systems, with the region of zero conductance resultingfrom a Coulomb-gap at the Fermi level. These are remarkable resultsgiven the simple method of sample fabrication and the fact that themeasurements were made at 300 K. One intriguing feature is the voltagescale of the conductance structure, which is considerably larger thancommonly found in other single-electron systems.

Example 10

[0182] This example concerns the morphology ofnanoparticle/poly-L-lysine (PLL) assemblies. Samples for morphologicalstudies were prepared on mica substantially as described above inExample 10. The assemblies were imaged using tapping mode AFM. Theinitial, dried PLL.HBr films were found to be smooth with voids probablydue to film contraction while drying. During the deprotonation step, PLLis removed and the film becomes more porous, leading to a submonolayerlattice of PLL aggregate. Upon decoration with functionalizednanoparticles, extended, chain-like assemblies were observed. See FIG.15. Thus, by this method, low dimensional nanoparticle arrays can bemade, which allows production of a system having useful electricalproperties as opposed to systems comprising monolayers of material.

[0183]FIG. 15 also raises the issue of the effects of disorder anddefects. There are two main types of disorder experienced with thedisclosed systems, positional disorder and particle size dispersion.FIG. 15 shows that the illustrated embodiment has nanoparticles that arenot evenly spaced one from another. This is referred to herein aspositional disorder. In traditional semiconductor structures, there isno tolerance for unequal spacing of the metal islands. However, with thesmall dimensions of the disclosed systems, the electrical properties donot depend on the spacing between cluster. Another potential disorder isparticle size dispersion, which can adversely affect the usefulelectrical properties of the described systems.

[0184] The described wet chemical fabrication method produces quasi,one-dimensional structures consistent with the morphology suggested bythe current scaling above threshold. The surface coverage of thesestructures is low, far below that required for a continuous path to beformed between the electrodes. This observation rules out thepossibility that bottleneck regions, or a single pathway dominate theelectrical behavior. Individual nanoparticles also are found on thesurface after chemical fabrication. Their low area density gives anaverage separation considerably larger than the distance between thenanoparticles forming the extended chains. Thus, the isolatednanoparticles are unlikely to contribute to the overall electricalbehavior. The electrical properties suggest single-electron effects inone-dimensional structures and the AFM images show that the fabricationmethod is capable of producing such structures. However, there is anapparent discrepancy between the disordered nature of the sample seen byAFM (a collection of randomly sized, placed and oriented nanoparticlearrays) and the clearly defined, periodic conductance features in theelectrical characteristics that suggest an ordered system. Theelectrical behavior of randomly oriented nanoparticle arrays thatcontain defects has been calculated. Periodic conductance features occurdespite the presence of defects and that surface conduction inconjunction with conduction through the array explains the large voltagescale found in the data.

[0185] Single-electron charging effects are governed by the capacitancebetween adjacent nanoparticles and the capacitance of each nanoparticleto a ground plane. The nanoparticles can be treated as identical metalspheres of radius 0.7 nm surrounded by a homogeneous ligand shell with adielectric constant of 3. Including the ligand shell, the minimumcenter-to-center separation is 4.2 nm. Calculating the capacitancematrix for a row of nanoparticles the interparticle capacitance wasdetermined to be Cdd≈0.04 aF and a capacitance to ground C_(g)≈0.17 aF.Thus, the dimensions of these nanoparticle building blocks result in aregime where C_(g)>C_(dd), which is opposite to that studied in mostlithographically defined systems. The capacitance values imply that thetotal capacitance of a nanoparticle is dominated by C_(g) and thecalculated value shows that the 5 electrostatic charging energye²/2C_(g) is more than an order of magnitude larger than k_(B)T at 300K, consistent with Coulomb blockade effects at room temperature.

[0186] Numerical simulations of perfect chains confirm that thresholdbehavior, linear scaling above threshold and a Coulomb staircase can allbe expected at room temperature. To simulate the number of conductancepeaks observed, a minimum of four particles is required in a chain.While the expected and experimental values of the ratio ΔV/V_(T) agree,there is a discrepancy in the absolute voltage values for the thresholdand the periodicity. The anticipated value of V_(T)≈e/2C_(g)=0.47 V ismore than a factor of twenty smaller than the measured value. ReducingC_(g) will increase V_(T). However, assuming that at very smalldimensions the capacitance still can be estimated from the geometry of aparticle, the reduction in C_(g) necessary to explain the data wouldrequire nanoparticles with unphysically small radii. From this argumentit appears that the conduction path must include potential drops thatmay be the result of contact resistance between the electrodes and thenanoparticle system, surface conduction, weak links within the networkitself, or a combination of all three.

[0187] The presence of radio frequency (RF) signals and other phenomena,such as quantum size effects and the physical motion of nanoparticles ina field (the shuttle mechanism) also can introduce conductance features.RF signals applied to the sample had no perceivable affect on theconductance structure. Quantum size effects are weak at room temperatureand the energy level structure is highly dependent on the structure ofthe nanoparticles, the ligands and the coupling between particles. Thus,it seems unlikely that resonant tunneling through discrete electroniclevels is the cause of the regularly spaced structure we observe. Ashuttle mechanism is ruled out because it predicts structure equallyspaced in current rather than in voltage as found with the presentsystems. For the I-V characteristics measured, this mechanism also wouldrequire vibrational frequencies that are much lower than is reasonablefor the properties of the ligand.

[0188] Given the preparation method and the large area (˜3 mm² ) sampledby the IDA electrodes, disorder and spatial averaging are expected inthe samples. The types of disorder expected to have the greatestinfluence on the electrical properties are variations in core size thatinfluence C_(g) and the particle-particle spacing (positional disorder)that affects Cdd. In addition, the effects of particle chain length andchain orientation must be considered. Numerical simulations were used toexplore these effects individually and in combination. Chains of betweenfour and nine particles whose core radii were randomly dispersed by upto ±30% (the measured value) showed conductance structure that wasperiodic to within the measurement uncertainty (±12%). For chains thatcontain ten or more particles, the uncertainty in the periodicity wasmuch larger than measured. Similarly, when the radius dispersion wasincreased to ±50% the position of the conductance peaks was found tochange significantly and the ratio ΔV/V_(T) deviated markedly from avalue of two. Dispersion in C_(dd) due to a distribution ofparticle-particle spacings was found to have little effect on thefeatures. This is not surprising for a system in which C_(g)>C_(dd)since the conductance is relatively insensitive to the inter-particlecapacitance. From this analysis it appears that individual,one-dimensional chains containing less than ten particles with ±30%radius variation can support Coulomb staircase behavior.

[0189] When many chains are in parallel the periodicity is maintainedprovided the chain lengths have a narrow distribution, implying that thesamples contain chains of a well-defined length. This length may arisefrom individual PLL chains that, based on their molecular weight, canaccommodate seven or eight nanoparticles. Given length uniformity,angular averaging over all possible orientations of a perfect chainbetween the electrodes does not remove the conductance peaks, but doesbroaden them and increases the conductance in the valleys between peaks.When core size dispersion (±30%) and orientation averaging are combined,the simulations still predict periodicity in the conductance. For thesesimulations 756 chains each having a different randomized set ofcapacitances and a different orientation were used. Interestingly, evenwith this degree of averaging, residual conductance periodicity is stillfound. While a direct comparison with the measured data cannot be made,it appears as if the amount of disorder used in the simulationsoverestimates the actual degree of disorder in the samples.

[0190] Finally, note that the nature of the current path and the factthat the measured voltage scale of the Coulomb blockade structuredisagrees with the value determined from the capacitance. The conductionprocess must involve both the chains and the surface of the substrate.The origin of the surface conductance is likely a thin water layer,which is known to have Ohmic behavior and is expected given the wetchemical preparation method. The surface conductance is the backgroundthat is removed from the data and is the means by which chains, arrangedrandomly on the surface, are electrically connected. Once the potentialdrop across a chain reaches the threshold value, the chain will come outof blockade and become part of the conduction path. Given that thechains are short compared to the inter-electrode spacing and that theredoes not appear to be a continuous path between the electrodes, thepoint at which a chain begins to conduct is a particular fraction of theapplied voltage: that is, the surface conductance behaves in the mannerof a potential divider which provides an explanation for the differencebetween the predicted and observed scales. It is known that theinterparticle spacing in ordered arrays of nanoparticles plays a role inthe nature of the electrical transport. In certain embodiments of thearrays described herein the ligands provide a core separation thatsuggests electron hopping is the process responsible for chargetransfer. In this case, transport will be dominated through chains thathave the lowest potential barriers between nanoparticles. Defects areexpected to increase the potential barrier. Hence, chains that have thefewest missing or misplaced nanoparticles (defects) will govern thetransport properties.

[0191] The wet chemical process has been used to produce extendednanoparticle arrays on biopolymer templates between electrode pairs. TheI-V characteristics show clear evidence for single-electron chargingeffects in transport that is limited to one-dimension. From the computedcapacitance values and numerical simulations the chains likely containbetween four and nine nanoparticles and that the I-V behavior of anensemble of chains interconnected by the surface conduction of thesubstrate is tolerant toward variations of chain orientation, core sizeand inter-particle spacing. The measurements reported here used indirectelectrical contact to an ensemble of nanoparticle arrays. This suggeststhat similar contact techniques which avoid alignment between electrodesand nanoparticles will be useful in their future electricalcharacterization and application.

Example 11

[0192] This example concerns using DNA as a scaffold for receivingnanoparticles. Thin macroscopic gold or silver pads are deposited ontofreshly cleaved mica through a shadow mask that defines contacts. Vacuumannealing is used, where necessary, to produce extremely flat metalsurfaces. Silver is preferred because it does not interfere with thedetection of gold particles on the surface by XPS. Purified lambda DNA(a Hind III digest from New England BioLabs, Inc consists of eightfragments of defined length, ranging from 42-7,800 nm) is deposited ontothe mica substrate in the presence of Mg²⁺ that serves to bind the DNAto the mica such that the DNA double strands are extended along thesurface. Some of these strands rest partially on the gold pads andpartially on the mica surface. These samples, after rinsing and drying,are used for control experiments and as templates for assembling thegold nanoparticles. Individual undecorated double-stranded DNA chainsare identified by AFM. A survey of the periphery of the electrodecontact pads reveals the number of appropriate strands on the surfaceand aids in optimizing the deposition conditions.

[0193] Functionalized nanoparticles for assembly on the DNA templatesare prepared as described herein. For example, one embodiment of such amethod was used to make functionalized, 1.5 nm diameter goldnanoparticles. The reaction conditions were: a) two-phase mixture oftoluene and water, one equivalent tetraoctylammonium bromide, 10equivalents, sodium borohydride, and b) either a single-phase ligandexchange with an organic solution of a thiol or a two-phase exchangebetween Au-TPP in organic solvent and a water-soluble thiol in aqueoussolution.

Example 12

[0194] This example describes a method for making an intentionallycrossed junction of DNA-templated, one-dimensional, nanoparticleassemblies. DNA is first attached to an electrode, such as by using athiol linkage. The DNA is then correctly aligned by flow-inducedalignment of the DNA strand. The DNA strand is bound to the micasurface, such as by using Mg²⁺. Cationic nanoparticles are depositedonto the DNA template, and the DNA is attached to the adjacentelectrode. A second DNA strand is aligned by flow-induced alignmentorthogonal to the first DNA strand. The second DNA strand binds to thecationic nanoparticles on the first DNA strand. Additional cationicnanoparticles may be deposited onto the new DNA strand to form anintentionally crossed junction of DNA-templated, one-dimensionalnanoparticle assemblies.

[0195] In another embodiment, complex DNA architectures, such asHolliday junctions are used as the scaffold for creating patterns ofnanoparticles between electrodes. Assembly of branched structures onelectrode patterned surfaces provide a method for assembling gates ofelectronic dimensions. For example crossed strands of nanoparticles,where the two strands are produced from nanoparticles of differingradii, may be used to produce a molecular-scale gate for the strandhaving the smaller radius nanoparticles.

Example 13

[0196]FIG. 16 illustrates that the poly-L-lysine templated sample has astable and reproducible voltage response, and that the response of thesystem does not decay over time. In contrast, when a template is notused and a non-patterned system formed, the response decays. Thus, thetemplate stabilizes the voltage response, likely because the particlesare in fixed positions, and hence such systems are electrically morestable than systems that are not patterned.

[0197] The disclosed embodiments provide a novel approach to providingstructures having well defined electrical properties. Coulomb blockadeat room temperature is routinely observed in these systems, and theCoulomb blockade response is stabilized using biopolymer templating.And, single-electron charging effects in one-dimensional pathways areremarkably tolerant of defects and disorder.

[0198] The present invention has been described with reference topreferred embodiments. Other embodiments of the invention will beapparent to those skilled in the art from a consideration of thisspecification or practice of the invention disclosed herein. It isintended that the specification and examples be considered as exemplaryonly, with the true scope and spirit of the invention being indicated bythe following claims.

We claim:
 1. A method for forming arrays of metal, alloy, semiconductorand/or magnetic clusters, comprising: placing a scaffold on a substrate;and coupling monodispersed clusters, selected from the group consistingof metal clusters, alloy clusters, semiconductor clusters, magneticclusters, and combinations thereof, to the scaffold.
 2. The method ofclaim 1, wherein coupling comprises contacting the scaffold withclusters having plural exchangeable ligands, where at least one of theligands is exchanged for a functional group of the scaffold.
 3. Themethod of claim 1, wherein coupling comprises contacting the scaffoldwith clusters having plural ligands, where at least one of the ligandsis charged and is electrostatically attracted to a scaffold of oppositecharge.
 4. The method of claim 3, wherein the scaffold is positivelycharged polylysine and the plural ligands of the clusters include atleast one having a negatively charged group.
 5. The method of claim 4,wherein the negatively charged group is selected from the groupconsisting of carboxylate, sulfonate, and combinations thereof.
 6. Themethod of claim 4, wherein the polylysine is poly-L-lysine.
 7. Themethod of claim 3, wherein the scaffold is a polynucleotide having anegatively charged phosphate backbone and the plural ligands of theclusters include at least one having a positively charged group selectedfrom the group consisting of protonated amine groups, quaternaryammonium groups, and combinations thereof.
 8. The method of claim 1,wherein coupling comprises contacting the scaffold with clusters havingplural ligands, where at least one of the ligands becomes associatedwith the scaffold through a hydrophobic interaction.
 9. The method ofclaim 8, wherein the scaffold is a polynucleotide and the plural ligandsof the clusters include at least one ligand that intercalates into thepolynucleotide.
 10. The method of claim 9, wherein the polynucleotide isDNA.
 11. The method of claim 1, wherein placing the scaffold on thesubstrate comprises placing the scaffold on the substrate in apredetermined pattern.
 12. The method of claim 11, wherein placing thescaffold on the substrate in a predetermined pattern comprises aligningthe scaffold in an electric field created between electrodes on thesubstrate.
 13. The method of claim 12, wherein the scaffold has anelectric dipole moment that causes the scaffold to align in the electricfield.
 14. The method of claim 13, wherein the scaffold is a helicalpolynucleotide.
 15. The method of claim 13, wherein the scaffold is ahelical polypeptide.
 16. The method of claim 15, wherein the helicalpolypeptide is in the form of an α-helix.
 17. The method of claim 16,wherein the polypeptide is polylysine.
 18. The method of claim 11,wherein placing the scaffold on the substrate in a predetermined patterncomprises polymerizing monomers, oligomers, or polypeptides into largerpolypeptides to form a scaffold between two electrodes on the surface ofthe substrate.
 19. The method of claim 11, wherein placing the scaffoldon the substrate in a predetermined pattern comprises anchoring thescaffold and inducing alignment of the anchored scaffold in a particulardirection by fluid flow.
 20. The method of claim 19, wherein thescaffold is attached to a first electrode and aligned by fluid flow,substantially in the direction of a second electrode.
 21. The method ofclaim 20, wherein a second scaffold is attached to a third electrode andaligned by fluid flow such that the second scaffold crosses the scaffoldaligned between the first and second electrodes.
 22. The method of claim21, wherein the second scaffold is aligned between the third electrodeand a fourth electrode.
 23. The method of claim 10, wherein placing thescaffold on the substrate in a predetermined pattern comprises aligninga scaffold having a magnetic moment in a magnetic field.
 24. The methodof claim 1, wherein the clusters comprise metal clusters, and the metalis selected from the group consisting of Au, Ag, Pt, Pd, and mixturesthereof.
 25. The method according to claim 24, wherein the metal clusteris Au₅₅.
 26. The method according to claim 1, wherein the scaffoldcomprises molecules selected from the group consisting ofpolynucleotides, polypeptides, and mixtures thereof.
 27. The methodaccording to claim 26, wherein the scaffold comprises polypeptidescapable of forming α helices.
 28. The method according to claim 27,wherein the polypeptide is polylysine.
 29. The method according to claim1, wherein the clusters are semiconductors selected from the groupconsisting of cadmium selenide, zinc selenide, cadmium sulfide, cadmiumtelluride, cadmium-mercury-telluride, zinc telluride, gallium arsenide,indium arsenide and lead sulfide.
 30. The method according to claim 1,wherein placing the scaffold comprises aligning the polypeptides betweenelectrodes on the substrate.
 31. The method according to claim 1,wherein placing the scaffold on the substrate comprises polymerizingmonomers, oligomers or polypeptides into larger polypeptides on thesubstrate.
 32. A method for forming arrays of metal clusters,comprising: placing a scaffold on a substrate, the scaffold comprisingmolecules selected from the group consisting of polynucleotides,polypeptides, and mixtures thereof; and forming arrays by contacting thescaffold with plural monodispersed ligand-stabilized metal clusters, themetal being selected from the group consisting of Ag, Au, Pt, Pd andmixtures thereof, the clusters being coupled to the scaffold.
 33. Themethod according to claim 32, wherein the scaffold comprisespolypeptides capable of forming α helices.
 34. The method according toclaim 33, wherein the polypeptide is polylysine.
 35. The methodaccording to claim 32, wherein the scaffold is DNA.
 36. The methodaccording to claim 35, wherein the DNA is a Holliday junction.
 37. Themethod according to claim 32, wherein the clusters are coupled to thescaffold by a coupling method selected from the group consisting ofligand exchange reactions, electrostatic interactions, hydrophobicinteractions, intercalation interactions, covalent bonds, andcombinations thereof.
 38. The method according to claim 32, whereinplacing the scaffold on the substrate comprises aligning the scaffoldbetween electrodes on the substrate.
 39. The method according to claim38, wherein aligning the scaffold between electrodes comprises aligningthe scaffold by creating an electric field between the electrodes. 40.The method according to claim 38, wherein aligning the scaffold betweenelectrodes comprises aligning the scaffold by anchoring a first end ofthe scaffold to a first electrode and creating fluid flow in thedirection of a second electrode such that the scaffold becomessubstantially aligned with the direction between the first and secondelectrodes.
 41. The method according to claim 38, wherein placing thescaffold on the substrate comprises polymerizing monomers, oligomers orpolypeptides into larger polypeptides between electrodes on thesubstrate.
 42. A composition, comprising: a polypeptide capable offorming α-helix; and plural monodispersed clusters, each cluster havingplural ligands that serve to couple the clusters to the polypeptide. 43.The composition of claim 42, wherein the plural ligands of the clustersinteract with the polypeptide by an interaction selected from the groupconsisting of ligand exchange reactions, electrostatic interactions,hydrophobic interactions, and combinations thereof.
 44. The compositionaccording to claim 42, wherein the clusters comprise metal and/orsemiconductor clusters having radii of from about 0.4 nm to about 1.8nm.
 45. The composition according to claim 44, wherein the metal and/orsemiconductor clusters have radii of from about 0.4 to about 1.0 nm. 46.The composition according to claim 42, wherein the clusters comprisemetal clusters, and the metal is selected from the group consisting ofAu, Ag, Pt, Pd and mixtures thereof.
 47. The composition according toclaim 46, comprising Au₅₅ metal clusters.
 48. A composition, comprising:a polynucleotide capable of forming a helical structure; and pluralmonodispersed clusters, each cluster having plural ligands that serve tocouple the clusters to the polynucleotide.
 49. The composition of claim48, wherein the plural ligands of the clusters interact with thepolynucleotide by an interaction selected from the group consisting ofligand exchange reactions, electrostatic interactions, hydrophobicinteraction, intercalation reactions and combinations thereof.
 50. Thecomposition according to claim 48, wherein the clusters comprise metaland/or semiconductor clusters having radii of from about 0.4 nm to about1.8 nm.
 51. The composition according to claim 48, wherein the clusterscomprise metal clusters, and the metal is selected from the groupconsisting of Au, Ag, Pt, Pd and mixtures thereof.
 52. An organizedarray of metal clusters, comprising: monodispersed, ligand-stabilizedmetal clusters having metal-cluster radii of from about 0.4 nm to about1.8 nm, the metal being selected from the group consisting of Ag, Au,Pt, Pd and mixtures thereof; and a scaffold, the metal clusters beingcoupled to the scaffold to form an organized array.
 53. The arrayaccording to claim 52, wherein the scaffold comprises molecules selectedfrom the group consisting of polynucleotides, polypeptides, and mixturesthereof.
 54. The array according to claim 53, wherein the scaffoldcomprises polypeptides capable of forming α helices.
 55. The arrayaccording to claim 53, wherein the scaffold comprises helical DNA. 56.An electronic device that operates at or about room temperature based onthe Coulomb blockade effect, comprising: a first cluster comprising ametal cluster core having a radius of between about 0.4 nm and about 1.8nm; and a second such cluster physically spaced apart from the firstmetal cluster at a distance of less than about 5 nm, where the physicalseparation between the first and second clusters is maintained by theclusters being coupled to a biomolecular scaffold.
 57. The electronicdevice of claim 56, comprising first and second biomolecular scaffolds,each with coupled clusters, where the first and second scaffoldsintersect.
 58. The electronic device of claim 56, where the deviceexhibits a linear increase in the number of electrons passing betweenthe first and second clusters as the potential difference between thetwo clusters is increased above a threshold value.
 59. A method ofsynthesizing phosphine-stabilized gold nanoparticles, comprising:dissolving HAuCl₄ and PPh₃ in a biphasic system, the biphasic systemcomprising a water phase, an organic phase, and a phase transfercatalyst; and adding sodium borohydride to the biphasic system.
 60. Themethod of claim 59, wherein the biphasic system comprises water and anorganic solvent selected from the group consisting of toluene, xylenes,benzene, and mixtures thereof.
 61. The method of claim 59, wherein thephase transfer catalyst is a quaternary ammonium salt.
 62. The method ofclaim 61, wherein the phase transfer catalyst is tetraoctylammoniumbromide.
 63. The method of claim 59, wherein the size of thephosphine-stabilized gold nanoparticles may be controlled by the rate atwhich sodium borohydride is added to the biphasic system.
 64. A methodof preparing thiol-stabilized gold nanoparticles, comprising: dissolvinga phosphine-stabilized gold nanoparticle in an organic solvent; andexchanging the phosphine ligands of the phosphine-stabilized goldnanoparticle for thiol ligands, the thiol ligands further comprising agroup of atoms that is capable of coupling the thiol-stabilized goldnanoparticle to a scaffold.
 65. The method of claim 64, whereinexchanging the phosphine ligands for thiol ligands comprises dissolvingthe thiol ligand in the organic solvent.
 66. The method of claim 65,wherein the organic solvent is water-immiscible and exchanging thephosphine ligands for thiol ligands comprises dissolving the thiolligand in water and contacting the water with the organic solvent toform a biphasic system.